Patterning and Cell Type Specification in the Developing CNS and PNS: Comprehensive Developmental Neuroscience

Cover
Patterning and Cell Type Specification in the Developing CNS and PNS
Copyright
Contributors
Part I: Induction and patterning of the CNS and PNS
1 - Morphogens, patterning centers, and their mechanisms of action
	1.1 General principles of morphogen gradients
		1.1.1 History of the morphogen and morphogenetic field
		1.1.2 How morphogen gradients pattern tissues
		1.1.3 How morphogens are distributed
		1.1.4 How morphogen signaling is transduced and interpreted
		1.1.5 How morphogen gradients are converted into sharp boundaries
		1.1.6 Summary-general principles of morphogen gradients
	1.2 Local signaling centers and probable morphogens in the telencephalon
		1.2.1 Early forebrain patterning
		1.2.2 The RPC
		1.2.3 The telencephalic roof plate and cortical hem
		1.2.4 The antihem
	1.3 BMPs as morphogens in telencephalic patterning
		1.3.1 Performance objectives for a BMP gradient in the dorsal telencephalon
		1.3.2 Midline expression and homeogenetic expansion of BMP production
		1.3.3 BMP signaling gradient in the dorsal telencephalon
		1.3.4 BMPs as dorsal telencephalic morphogens
		1.3.5 Linear conversion of BMP signaling by cortical cells
		1.3.6 Nonlinear conversion of BMP signaling by DTM cells
		1.3.7 Summary-the BMP signaling gradient
	1.4 FGF8 as a morphogen in telencephalic patterning
	1.5 Interactions among signaling centers in telencephalic patterning
		1.5.1 FGF8, Shh, and BMP signaling
		1.5.2 Cross-regulation of BMP, FGF, and WNT signaling
		1.5.3 Interactions of Shh, FGFs, and Gli3
	1.6 Morphogens in human brain disease
		1.6.1 Holoprosencephaly and Kallmann syndrome
		1.6.2 Gradients in holoprosencephaly neuropathology
		1.6.3 Gradients in other human brain disorders
	References
2 - Telencephalon patterning
	2.1 Introduction
	2.2 Telencephalon induction
		2.2.1 The anterior neural ridge
		2.2.2 FGF signaling
		2.2.3 Wnt antagonism
		2.2.4 Interactions of low Wnt with FGFs and BMPs
	2.3 Overview of early telencephalic subdivisions
	2.4 Establishing dorsal versus ventral domains
		2.4.1 Shh and Gli3, two key players
		2.4.2 Foxg1 and FGFs cooperatively promote ventral development
		2.4.3 Establishing the dorsal telencephalic domain
		2.4.4 Sharpening the dorsal-ventral border
		2.4.5 The olfactory bulbs
	2.5 Boundary structures as organizing centers and CR cell sources
		2.5.1 Nomenclature of domains in the early telencephalic neuroepithelium
		2.5.2 Specification of the hem and the antihem
			2.5.2.1 Molecular mechanisms that act to position and specify the cortical hem
			2.5.2.2 Molecular mechanisms that act to specify and position the antihem
		2.5.3 Cajal-Retzius cells arise from four telencephalic boundary structures
		2.5.4 Organizer functions of telencephalic boundary structures
			2.5.4.1 Rostral signaling center/septum
				2.5.4.1.1 Hem
			2.5.4.2 Antihem
	2.6 Subdividing ventral domains
		2.6.1 The striatum and pallidum
		2.6.2 The amygdala
		2.6.3 An evolutionary perspective for how the neocortex arose
		2.6.4 Lineage and fate mapping in the ventral telencephalon
	2.7 Conclusions
	Acknowledgments
	References
3 - Area patterning of the mammalian neocortex
	3.1 Introduction
		3.1.1 Basic principles
		3.1.2 Classic neocortical area patterning models
	3.2 Indications that intrinsic mechanisms pattern the neocortical primordium
	3.3 Morphogens impart position to the neocortical primordium
		3.3.1 Morphogen signaling
		3.3.2 Neocortical patterning by FGFs
		3.3.3 Fgf8 regulates neocortical guidance of thalamic axons
		3.3.4 Neocortical patterning by the cortical hem
	3.4 Patterning genes downstream of morphogen signaling
		3.4.1 Emx2 and Pax6
		3.4.2 Dmrt5/Dmrta2
		3.4.3 Couptf1/Nr2f1
		3.4.4 Sp8
		3.4.5 Pbx
	3.5 Do neocortical areas arise from dedicated progenitor cell pools?
		3.5.1 Transcription factors known to pattern the NP appear in gradients, not domains
		3.5.2 Mapping the cortical primordium with forebrain enhancers
	3.6 The influence of thalamic innervation
		3.6.1 Guidance of thalamocortical axons and area formation
		3.6.2 Thalamic innervation determines the function of a cortical area
		3.6.3 Effects of thalamocortical afferents on area size and cortical progenitor cells
		3.6.4 Thalamic dependence of an area-specific feature
		3.6.5 Two mechanisms united
	3.7 Spontaneous activity and neocortical patterning
	3.8 Conservation of patterning mechanisms among different mammalian species
	3.9 Conclusions
	References
4 - Patterning of thalamus
	4.1 Introduction
	4.2 Insights into diencephalic patterning
		4.2.1 Columnar and neuromeric models
		4.2.2 Morphologic segmentation of the diencephalon in the prosomeric model
		4.2.3 Molecular regionalization of the diencephalon
			4.2.3.1 Prosomere 1
			4.2.3.2 Prosomere 2: the epithalamic domain
			4.2.3.3 Prosomere 3
	4.3 Prosomere 2: the thalamic domain
		4.3.1 Cell lineages in the p2 alar plate
		4.3.2 Signaling molecules during the initial patterning phase
			4.3.2.1 Shh
			4.3.2.2 Wnt
			4.3.2.3 Fibroblast growth factor
		4.3.3 Transcription factor control for neuronal identity
	List of acronyms and abbreviations
	References
5 - Midbrain patterning: polarity formation of the tectum, midbrain regionalization, and isthmus organizer
	5.1 Introduction: brief description about midbrain
	5.2 Tectum laminar formation
	5.3 Optic tectum as a visual center for the lower vertebrate
		5.3.1 Retinotectal projection in a retinotopic manner
		5.3.2 Polarity formation in the optic tectum
	5.4 Development of midbrain from the mesencephalic brain vesicle
		5.4.1 Transcription factors that determine the midbrain
		5.4.2 Midbrain-hindbrain boundary formation
		5.4.3 Diencephalon-mesencephalon boundary formation
		5.4.4 Dorsoventral patterning in the midbrain
	5.5 Isthmus organizer
		5.5.1 Isthmus emanates organizing signal
		5.5.2 Competence of the neural tube to Fgf8 signaling is determined by preexisting transcription factors
		5.5.3 Intracellular signal transduction
		5.5.4 How tectum and cerebellum are organized by isthmus organizing signal?
	5.6 Concluding remarks
	List of abbreviations of genes and molecules
	List of abbreviations (general)
	Glossary
	References
6 - Cerebellar patterning
	6.1 Introduction
	6.2 Early formation of cerebellum
		6.2.1 Morphogenetic aspect of first steps of cerebellar formation
		6.2.2 Molecular mechanisms underlying initial formation of cerebellum
	6.3 Three types of cerebellar patterning in adult mammals
		6.3.1 Cerebellar anterior-posterior patterning
			6.3.1.1 Lobes
			6.3.1.2 Lobules (I-X)
			6.3.1.3 Functional roles of lobes
		6.3.2 Cerebellar medial-lateral patterning
			6.3.2.1 Parasagittal zones
			6.3.2.2 Parasagittal stripes
			6.3.2.3 Correspondence between parasagittal zones and parasagittal stripes
			6.3.2.4 Functional roles of parasagittal zones and stripes
		6.3.3 Cerebellar outer-inner patterning
			6.3.3.1 The molecular layer
			6.3.3.2 The Purkinje cell layer
			6.3.3.3 The granular layer
			6.3.3.4 The white matter
			6.3.3.5 The cerebellar nuclei
			6.3.3.6 Roles of cerebellar outer-inner patterning
	6.4 Formation of cerebellar patterning
		6.4.1 Formation of cerebellar anterior-posterior patterning
			6.4.1.1 Formation of lobes and lobules
			6.4.1.2 Cellular mechanisms underlying the formation of lobes and lobules
		6.4.2 Formation of cerebellar medial-lateral patterning
			6.4.2.1 Formation of parasagittal zones
			6.4.2.2 Cellular and molecular mechanisms underlying the formation of parasagittal zones
			6.4.2.3 Formation of parasagittal stripes
			6.4.2.4 Critical roles of Purkinje cell birth date in the formation of embryonic and adult parasagittal stripes and parasagittal zones
		6.4.3 Formation of cerebellar outer-inner patterning
			6.4.3.1 Formation of the molecular layer
			6.4.3.2 Formation of the Purkinje cell layer
			6.4.3.3 Formation of the granular layer
			6.4.3.4 Formation of the white matter and the cerebellar nuclei
			6.4.3.5 Mechanisms underlying the control of neuronal migration
			6.4.3.6 The deficits of neuronal migration by exposure to toxic substances and natural environmental factors result in abnormal O-I ...
	References
7 - Patterning and generation of neural diversity in the spinal cord
	7.1 Introduction
	7.2 Spatial signals and the generation of neuronal diversity
		7.2.1 Dorsoventral patterning and the induction of progenitor domains
			7.2.1.1 Induction of neural progenitor ventral fate: Shh signaling
			7.2.1.2 Induction of dorsal progenitor fate: Bmp and Wnt signaling
		7.2.2 Rostrocaudal patterning and regional identity
			7.2.2.1 Rostrocaudal antiparallel signaling
			7.2.2.2 Hox function in neuronal diversity
	7.3 Transcription factor combinatorial codes
		7.3.1 Transcriptional codes in spinal cord progenitor fate
		7.3.2 Transcription factor combinatorial codes in the diversification of postmitotic motor neurons
		7.3.3 Transcriptional signatures in spinal cord interneuron diversification
	7.4 Local signals and cell-cell interactions
		7.4.1 The role of notchdelta signaling in interneuron and motor neuron subtype specification
		7.4.2 Retinoid signaling in motor neuron subtype specification
	7.5 Temporal signals in the specification of spinal cord glia
		7.5.1 Specification of oligodendrocytes
		7.5.2 Astrogenesis in the spinal cord
	7.6 Application of spinal cord developmental programs to advance therapies for human diseases
	7.7 Conclusions
	List of abbreviations
	Glossary
	References
8 - Formation and maturation of neuromuscular junctions
	8.1 Introduction
	8.2 The neuromuscular junction is comprised of three cell types
	8.3 Origin and initial interaction among cells that form the neuromuscular junction
	8.4 Formation of a differentiated postsynaptic membrane: the agrin-MuSK hypothesis
	8.5 Interplay between agrin and ACh in sculpting the postsynaptic region
	8.6 Molecules involved in nAChR prepatterning
	8.7 Additional molecules important for clustering and stabilizing developing neuromuscular junctions
	8.8 Synapse elimination at the neuromuscular junction
	8.9 Synapse elimination: structural and functional changes at neuromuscular junctions
	8.10 Synapse elimination: activity-dependent competition and molecular mechanisms
	8.11 Synapse elimination: role of T/PSCs
	8.12 Maturation and maintenance of neuromuscular junctions
	8.13 Summary
	List of abbreviations
	References
9 - Neural induction of embryonic stem/induced pluripotent stem cells
	9.1 Introduction
	9.2 Introduction to embryonic stem cells and induced pluripotent stem cells
		9.2.1 Reprogramming
		9.2.2 Discovery of induced pluripotent stem cells
	9.3 Neural induction
	9.4 Patterning of neural progenitors
		9.4.1 Neuronal progenitor specification along the D-V axis
		9.4.2 Neuronal progenitor specification along the A-P axis
		9.4.3 Patterning using multiple morphogens gradients
		9.4.4 Temporal patterning
	9.5 Differentiation to specific regional identities
		9.5.1 Differentiation to forebrain cell types
			9.5.1.1 Cerebral cortex
			9.5.1.2 Hippocampus
			9.5.1.3 Basal ganglia
		9.5.2 Differentiation to midbrain cell types
		9.5.3 Differentiation to hindbrain cell types
		9.5.4 Differentiation to spinal cord cell types
	9.6 Differentiation to neural crest stem cells
	9.7 Differentiation to astrocytes and oligodendrocytes
		9.7.1 Astrocytes
		9.7.2 Oligodendrocytes
	9.8 Direct conversion of fibroblasts to induced neurons
	9.9 Conclusion
	Acknowledgment
	References
10 - Brain organoids as a model system for human neurodevelopment in health and disease
	10.1 Recapitulation of in vivo neurodevelopment
		10.1.1 Stage I: Neural induction and patterning
		10.1.2 Stage II: Lumen formation and apical-basal polarity
		10.1.3 Stage III: Proliferation of neural progenitors, interkinetic nuclear motion, and cortical expansion
		10.1.4 Stage IV: Neurogenesis, cortical layers formation, and neuronal migration
		10.1.5 Stage V: Neuronal maturation and network activity
		10.1.6 Evolutionary neurodevelopmental biology in organoids
	10.2 Organoids for neurodevelopmental disease modeling
		10.2.1 Modeling diseases associated with brain structure
			10.2.1.1 Microcephaly (small brains)-genetic mutations
			10.2.1.2 Microcephaly-ZIKA virus, mechanisms, and potential therapies
			10.2.1.3 Macrocephaly (large brains)
				10.2.1.3.1 Lissencephaly (smooth brain)
		10.2.2 Modeling of neuropsychiatric disorders
			10.2.2.1 Autism spectrum disorders and schizophrenia
	Acknowledgments
	References
11 - Formation of gyri and sulci
	11.1 Introduction
	11.2 Timing of the formation of gyri and sulci
	11.3 Cortical folding in evolution
	11.4 Cellular mechanisms of cortical folding
		11.4.1 Outer subventricular zone and basal progenitors
		11.4.2 Gene expression profiles
		11.4.3 Human- and primate-specific genes
		11.4.4 Differential growth and proliferation
			11.4.4.1 Cell cycle and the length of the neurogenic period
			11.4.4.2 Growth patterns
			11.4.4.3 Migration and cell adhesion
	11.5 Mechanical mechanisms
	11.6 Model systems in which to study cortical folding
		11.6.1 Cerebral organoids
		11.6.2 Ferret
		11.6.3 Nonhuman primates
		11.6.4 Human fetal tissue
	11.7 Neurodevelopmental disorders
		11.7.1 Lissencephaly
		11.7.2 Polymicrogyria
		11.7.3 Other folding disorders
	11.8 Conclusions
	Acknowledgments
	References
Part II: Generation of neuronal diversity
12 - Cell biology of neuronal progenitor cells
	12.1 Introduction
	12.2 Location of neuronal progenitors
		12.2.1 Multipotent progenitor cells in the ventricular zone generate CNS neurons
			12.2.1.1 Neuroepithelial cells
			12.2.1.2 Radial glia are neuronal progenitor cells
		12.2.2 Neuronal progenitor cells in the subventricular zone
		12.2.3 Other non-VZ/SVZ neuronal progenitor cells
			12.2.3.1 The dentate gyrus
			12.2.3.2 The external granule layer in the cerebellum
			12.2.3.3 The retina
		12.2.4 The peripheral nervous system
		12.2.5 Adult neurogenesis
	12.3 Creating different types of neuronal progenitor cells
		12.3.1 Neuronal progenitor diversification begins with a regional address
		12.3.2 Neuronal progenitor cells are specified temporally
			12.3.2.1 Temporal order of neuron generation in the cerebral cortex
		12.3.3 Molecular heterogeneity in neuronal progenitor cells
	12.4 Cell lineage analysis reveals the fate of individual neuronal progenitor cells
		12.4.1 Leading the way: cell lineage analysis in the invertebrate nervous system
		12.4.2 Cell lineage analysis in the mammalian nervous system
		12.4.3 Lineage analysis, the movie
	12.5 Structure and dynamism of neuronal progenitor cells
		12.5.1 Interkinetic nuclear migration
		12.5.2 Nuclear movement of non-APCs progenitor cells
		12.5.3 The structure of radial glia cells
			12.5.3.1 Apical-basal processes
			12.5.3.2 Adherens junctions
			12.5.3.3 Gap junctions
		12.5.4 Morphological transitions of neural progenitor cells
	12.6 Asymmetric cell division for neuronal diversity
		12.6.1 Establishing cell polarity and mitotic spindle orientation
		12.6.2 Spindle orientation and cell fate
		12.6.3 Asymmetric segregation of the centrosome and the primary cilium membrane
		12.6.4 Asymmetric inheritance of the midbody
		12.6.5 Asymmetric localization of cell fate determinants
	12.7 Progenitor microenvironment and regulating neuronal progenitor number
		12.7.1 Fgfs regulate brain size
		12.7.2 Shh and cerebellar granule neuron generation
		12.7.3 β-Catenin and Wnt pathway
		12.7.4 Apoptosis
	12.8 Summary
	Acknowledgments
	References
13 - Notch and neural development
	13.1 History of Notch signaling
	13.2 Molecular mechanisms
		13.2.1 Notch pathway components
		13.2.2 Ligand activation of the Notch receptor
		13.2.3 Notch and the balancing act
	13.3 Signaling diversity and cis-inhibition
	13.4 Timing and feedback are everything
	13.5 Notch and the maintenance of neural stem cells during nervous system development
	13.6 Notch and the generation of interneuron diversity
	13.7 Postnatal neurogenesis and gliogenesis
	13.8 Notch, glial cell fate, and maturation
	13.9 Notch and neuronal migration
	13.10 Notch and dendrite morphogenesis
	13.11 Synaptic plasticity and Notch signaling
	13.12 Embryonic stem cells and clinical perspectives
	13.13 Conclusion
	References
14 - bHLH factors in neurogenesis and neuronal subtype specification
	14.1 Overview of review content
	14.2 Identification of neural bHLH transcription factors: History and evolutionary conservation between fly and mammal
		14.2.1 The proneural bHLH factors
		14.2.2 The E-proteins: heterodimeric partners for proneural bHLH factors
		14.2.3 HES, HEY, and ID bHLH factors: inhibitors of neural differentiation
	14.3 bHLH factor function in neuronal differentiation
		14.3.1 Interplay between notch and proneural bHLH proteins
		14.3.2 Refinements in the models for transition from progenitor to differentiated neuron
	14.4 Functions of bHLH transcription factors in neuronal subtype specification
	14.5 Molecular characteristics of bHLH transcription factors
		14.5.1 Crystal structure of bHLH proteins: DNA recognition and dimer selectivity
		14.5.2 Structure function analysis of proneural bHLH proteins
	14.6 Protein-Protein interactions modulating cell type-specific functions of neural bHLH factors
	14.7 Transcriptional targets of proneural bHLH factors
	14.8 Transcriptional regulation of bHLH gene expression
	14.9 Posttranslational control of neural bHLH transcription factor function
	14.10 Reprogramming activities of proneural bHLH factors
	14.11 Perspective
	References
15 - The specification and generation of neurons in the ventral spinal cord
	15.1 Introduction and general organization
	15.2 Induction of spinal cord tissue and initiation of regional pattern
		15.2.1 The emergence and organization of cell subtypes in the ventral spinal cord
		15.2.2 Shh signaling and ventral cell fate specification
		15.2.3 Transcriptional control of progenitor gene expression
		15.2.4 Additional signaling influences over progenitor gene expression patterns
	15.3 Spinal cord neurogenesis
		15.3.1 Control of cell cycle progression and exit in neuronal progenitors
		15.3.2 Coordination of cell fate and neurogenesis
	15.4 The generation of differentiated neuronal cell subtypes
		15.4.1 Motor neuron axial subclass specification: rostral-caudal patterning of the spinal cord influences cell fate within a dorsa ...
		15.4.2 Genetic programs in postmitotic cells
		15.4.3 Motor neuron subclass diversification
		15.4.4 Correlation between cell fate and locomotor circuits
	References
16 - Neurogenesis in the cerebellum
	16.1 Introduction to the cerebellum
	16.2 Overview of cerebellar development
	16.3 Establishing the cerebellar territory
		16.3.1 Establishing the cerebellar territory along the anterior-posterior axis: the isthmic organizer
		16.3.2 Establishing the cerebellar territory along the dorsal-ventral axis
	16.4 The cerebellar ventricular zone and its derivatives
		16.4.1 Ventricular zone development and neurogenesis in ventricular zone
		16.4.2 Molecular mechanisms that regulate the differentiation and migration of Purkinje cells and GABAergic neurons of CN
		16.4.3 Molecular mechanisms that regulate development of PWM and GABAergic interneurons
	16.5 The cerebellar rhombic lip and its derivatives
		16.5.1 Rhombic lip induction and neurogenesis within the rhombic lip
		16.5.2 Regulation of granule cell development
			16.5.2.1 Regulation of tangential migration of granule neuron precursors from the rhombic lip
			16.5.2.2 Regulation of proliferation and differentiation of GNPs in the EGL
			16.5.2.3 Regulation of radial migration of granule cells from the EGL to the IGL
		16.5.3 Regulation of differentiation and migration of glutamatergic neurons of CN and UBCs
	16.6 Cerebellar stem cells and regeneration of the cerebellum
	16.7 Conclusions and future perspectives
	References
17 - The generation of midbrain dopaminergic neurons
	17.1 Introduction
		17.1.1 Dopamine
		17.1.2 Dopamine system in the brain
			17.1.2.1 Midbrain dopamine neurons-anatomically defined groups
			17.1.2.2 Midbrain dopamine neurons-groups defined by molecular profiles
	17.2 The development of midbrain dopaminergic neurons-general overview
	17.3 Generation of midbrain dopaminergic progenitors: patterning, specification, and proliferation
		17.3.1 Patterning
		17.3.2 Specification and proliferation
			17.3.2.1 The role of signaling centers and secreted factors
			17.3.2.2 The role of transcription factors
			17.3.2.3 Diversity in midbrain dopaminergic progenitors
	17.4 Generation of immature and mature midbrain dopaminergic neurons
		17.4.1 Regulation of maturation
		17.4.2 Migration of midbrain dopaminergic neurons
		17.4.3 Axonal pathfinding of midbrain dopaminergic neurons
	17.5 The terminal differentiation of the mature dopaminergic neuron
	17.6 Maintenance of midbrain dopaminergic neurons
	17.7 Perspectives
	References
18 - Neurogenesis in the basal ganglia
	18.1 Introduction
	18.2 Organization of embryonic subdivisions and their relationship to mature structures and cell types
		18.2.1 Subdivisions of the mature and embryonic basal ganglia
		18.2.2 Cellular organization of the developing basal ganglia
		18.2.3 Fate analysis of the GEs and their subdivisions
	18.3 Regional specification of subdivisions of the embryonic basal ganglia
		18.3.1 Morphogen and growth/differentiation factor signaling in the developing basal ganglia
			18.3.1.1 Shh signaling
			18.3.1.2 Receptor tyrosine kinase signaling
			18.3.1.3 Wnt signaling
			18.3.1.4 Tgf-β signaling
			18.3.1.5 Retinoid signaling
			18.3.1.6 Notch signaling
		18.3.2 Basal ganglia specification
		18.3.3 LGE and CGE specification
		18.3.4 MGE and POA specification
		18.3.5 Septum specification
	18.4 Generation of neuronal subtypes
		18.4.1 LGE and CGE neuronal derivatives
			18.4.1.1 Medium-sized striatal projection neurons
			18.4.1.2 Olfactory bulb interneurons
			18.4.1.3 Cortical and amygdalar interneurons
		18.4.2 MGE and POA neuronal derivatives
			18.4.2.1 Globus pallidus projection neurons
			18.4.2.2 Striatal interneurons
			18.4.2.3 Cortical interneurons
		18.4.3 Cis-regulatory elements and epigenetics of basal ganglia development
		18.4.4 Engineering basal ganglia neurons in vitro
	18.5 Summary
	References
19 - Specification of cortical projection neurons: transcriptional mechanisms
	19.1 Introduction
	19.2 Neocortical progenitors
	19.3 Neocortical progenitor cell-fate acquisition and plasticity
	19.4 Molecular controls over neocortical projection neuron subtype specification, development, and diversity
		19.4.1 Subtype specification of corticofugal projection neurons
		19.4.2 Subtype specification of callosal projection neurons
		19.4.3 Areal controls over diversity of neocortical projection neuron subtypes
	19.5 Progressive restriction and refinement of cortical projection neuron subtypes
	19.6 Generation of cortical projection neuron subtypes in vitro from human pluripotent stem cells
	19.7 Subtype-specific circuit wiring by growth cones
	19.8 Conclusions
	References
20 - The generation of cortical interneurons
	20.1 Diversity of mature cortical interneurons
		20.1.1 Parvalbumin interneurons
		20.1.2 Somatostatin interneurons
		20.1.3 Vasoactive intestinal peptide interneurons
		20.1.4 Lamp5 interneurons
		20.1.5 Gamma-synuclein and Serpinf1 interneurons
	20.2 Developmental origin of cortical interneurons
		20.2.1 The ventral origin of cortical neurons
		20.2.2 Genetic determinants involved in the specification of the MGE and CGE
		20.2.3 Place and time of origins of cortical interneurons
		20.2.4 Fate mapping strategies to assess the origin of cortical interneurons
		20.2.5 Genetic programs underlying the developmental emergence of interneurons
	20.3 Migration of cortical interneurons
		20.3.1 The influence of non-cell-autonomous signals on interneurons development
	20.4 Postnatal cortical interneuron development
		20.4.1 GABA is depolarizing during development
		20.4.2 Early patterns of network activity
		20.4.3 Role of activity in interneuron development
		20.4.4 Interneuron development and neurological disorders
	Acknowledgments
	References
21 - Specification of retinal cell types
	21.1 Introduction
	21.2 Retinal progenitor cell competence
		21.2.1 Establishment of retinal neuron and Müller glia birth order
		21.2.2 Clonal analyses in the developing retina
		21.2.3 Intrinsic versus extrinsic control of neurogenesis in the mammalian retina
	21.3 Intrinsic regulation of retinal development
		21.3.1 Early eye formation
		21.3.2 Retinal neurogenesis
		21.3.3 Intrinsic factor regulation of RGC development
		21.3.4 Intrinsic factors regulating photoreceptor development
		21.3.5 Epigenetic control of retinogenesis
		21.3.6 MicroRNA-mediated regulation of retinal genes
	21.4 Extrinsic regulation of retinogenesis
		21.4.1 Bmp/Tgfβ superfamily signaling
		21.4.2 Fgf signaling
		21.4.3 Notch signaling
		21.4.4 Retinoic acid signaling
		21.4.5 Hh signaling
		21.4.6 Wnt/β-catenin signaling
	21.5 Regenerative capacity of the retina
	21.6 Perspective
	Glossary
	References
22 - Neurogenesis in the postnatal V-SVZ and the origin of interneuron diversity
	22.1 Newborn neurons are generated in the V-SVZ of the adult brain
	22.2 Identification and origin of adult neural stem cells
	22.3 OB interneurons are heterogeneous
	22.4 Spatial specification of OB interneuron identity
	22.5 Temporal regulation of OB interneuron production
	22.6 Conclusion
	Acknowledgments
	References
23 - Neurogenesis in the damaged mammalian brain
	23.1 Introduction
	23.2 Persistent versus injury-induced neurogenesis in the adult brain
		23.2.1 Neurogenesis in the intact brain
			23.2.1.1 Active neurogenic regions
			23.2.1.2 Common and distinct features of adult neurogenic niches
			23.2.1.3 Cryptic or less active neurogenic regions
	23.3 Neurogenesis in the injured brain
		23.3.1 Stimulation of ongoing neurogenesis after damage
		23.3.2 Ectopic production of new neurons and glia in damaged brains
			23.3.2.1 Acute central nervous system injury
				23.3.2.1.1 Neocortex
				23.3.2.1.2 Striatum
				23.3.2.1.3 Hippocampus
				23.3.2.1.4 Substantia nigra
				23.3.2.1.5 Spinal cord
				23.3.2.1.6 Retina
				23.3.2.1.7 Other regions of the central nervous system
			23.3.2.2 Neurogenesis in chronic neurodegenerative conditions
				23.3.2.2.1 Alzheimer's disease
				23.3.2.2.2 Huntington disease
				23.3.2.2.3 Other neurodegenerative disorders
	23.4 Identity, integration, and extent of regeneration of new neurons
		23.4.1 Neocortex and hippocampus
		23.4.2 Striatum
		23.4.3 Other regions of the central nervous system
	23.5 Contribution of injury-induced neurogenesis to functional recovery
		23.5.1 Attenuation of neurogenesis
		23.5.2 Enhancement of neurogenesis
		23.5.3 Just a correlation or the cause?
	23.6 How widespread is injury-induced neurogenesis?: technical issues
	23.7 Cellular origins of injury-induced neurogenesis
		23.7.1 Contribution of NPCs in known neurogenic niches
		23.7.2 Identity of cells that generate new neurons
		23.7.3 Possible cellular sources outside neurogenic niches
	23.8 Gliogenesis after injury
		23.8.1 Oligodendrogenesis
		23.8.2 Astrogenesis
	23.9 Mechanisms underlying injury-induced neurogenesis
		23.9.1 Cell-intrinsic limitation of NPCs
			23.9.1.1 Limited number and expansion of NPCs
			23.9.1.2 Limited plasticity of NPCs
			23.9.1.3 Intrinsic fate determinants of NPCs
				23.9.1.3.1 Maintenance and proliferation of NSCs
				23.9.1.3.2 Differentiation of NSCs
				23.9.1.3.3 Neuronal subtype specification
		23.9.2 Environmental restrictions
			23.9.2.1 Growth factors
			23.9.2.2 Differentiation factors
			23.9.2.3 Migratory cues
			23.9.2.4 Survival and maturation signals
			23.9.2.5 Inflammatory and immune signals
			23.9.2.6 Neurotransmitter signals
				23.9.2.6.1 Glutamate and GABA
				23.9.2.6.2 Dopamine
				23.9.2.6.3 Serotonin
				23.9.2.6.4 Neuropeptides and other neurotransmitters
				23.9.2.6.5 Specific neuronal populations
			23.9.2.7 Hormones
			23.9.2.8 Other signals
				23.9.2.8.1 Nitric oxide
				23.9.2.8.2 Lipid mediators
				23.9.2.8.3 Cell grafts
	23.10 Neuronal cell reprogramming
	23.11 Link between neurodegeneration and neurogenesis
	23.12 Neurovascular niche
	23.13 Nonneurogenic roles of adult NPCs in brain repair
	23.14 Future perspectives
	Acknowledgments
	References
24 - Neuronal identity specification in the nematode Caenorhabditis elegans
	24.1 Introduction
	24.2 Neuron classification
	24.3 Neuronal cell lineages
	24.4 Genes controlling lineage decisions
		24.4.1 Neuronal versus nonneuronal lineage transformations
		24.4.2 Neuron lineage alterations and losses
	24.5 Terminal selectors control neuron class specification
	24.6 Genes controlling neuron subclass diversification
		24.6.1 Diversifying motor neuron classes
		24.6.2 Neuronal identity diversification across the left/right axis
	24.7 Other regulatory routines operating during neuronal differentiation
	24.8 Linking neuronal class specification to lineage
	24.9 Concluding remarks
	Acknowledgments
	References
25 - Development of the Drosophila melanogaster embryonic CNS: from neuroectoderm to unique neurons and glia
	25.1 Introduction
	25.2 Patterning of the neuroectoderm: breaking the homogeneity
		25.2.1 Patterning the ventral neuroectoderm
		25.2.2 Patterning the brain neuroectoderm
	25.3 Homologous neuromeres: same but different
	25.4 The chosen one: lateral inhibition
		25.4.1 Delamination of VNC neuroblasts
		25.4.2 Delamination of brain neuroblasts
	25.5 Unequal legacy: asymmetric cell division
	25.6 One thing at a time: the temporal cascade
	25.7 Regulation of neuroblast and daughter cell proliferation
		25.7.1 NB cell cycle exit and daughter cell proliferation switches: the role of cell cycle genes
		25.7.2 NB cell cycle exit and daughter cell proliferation switches: the role of late temporal and Hox genes
		25.7.3 NB exit and daughter cell proliferation switches: the role of the Notch pathway
		25.7.4 NB exit and daughter cell proliferation switches: the role of early temporal and pan-neural genes
		25.7.5 Brain-specific NB behavior: type II NBs
		25.7.6 Brain-specific NB behavior: mushroom body and IPC NBs
	25.8 The role of programmed cell death in the Drosophila embryonic VNC
	25.9 Finishing the picture: specification of unique cell types
		25.9.1 Specifying brain cells
		25.9.2 Specifying VNC neuropeptide cells
		25.9.3 Specifying motor neurons
		25.9.4 Specifying midline neurons
		25.9.5 Specifying glia cells
			25.9.5.1 Specifying lateral glia cells
			25.9.5.2 Specifying midline glia cells
	25.10 Conclusions
	25.11 Outstanding issues
	Acknowledgments
	References
26 - Neurogenesis in zebrafish
	26.1 Neural plate induction and patterning
		26.1.1 Formation of the neural tube
		26.1.2 Neural plate induction
		26.1.3 Neural plate patterning along the anteroposterior axis
	26.2 Establishment of the primary neuronal scaffold
		26.2.1 Organization of the primary neuronal scaffold
		26.2.2 Formation of the primary neuronal scaffold
			26.2.2.1 Identification of competent proneural domains within the neural plate
			26.2.2.2 Neurogenesis control within the proneural clusters
				26.2.2.2.1 Lateral inhibition in Drosophila
				26.2.2.2.2 Lateral inhibition in vertebrates
				26.2.2.2.3 Regulation of notch signaling
			26.2.2.3 Determination of primary neuronal identities
				26.2.2.3.1 Morphogens
				26.2.2.3.2 Notch signaling
	26.3 Secondary neurogenesis
		26.3.1 Functional anatomy of secondary neurogenesis
			26.3.1.1 Motor and sensory systems
			26.3.1.2 Neuromodulatory, neurohormone, and neuropeptide systems
		26.3.2 Molecular and cellular mechanisms of secondary neurogenesis
			26.3.2.1 Secondary neurogenesis: balance between proliferation and differentiation
			26.3.2.2 Neuroblast migration
				26.3.2.2.1 Facial branchiomotor neurons migration
				26.3.2.2.2 Migration of precursor cells in the cerebellum
			26.3.2.3 Neuronal subtype specification
				26.3.2.3.1 Specification of subtypes in the spinal cord
				26.3.2.3.2 Neuromodulatory systems
					26.3.2.3.2.1 DA neurons
					26.3.2.3.2.2 NA neurons
					26.3.2.3.2.3 5-HT and HA neurons
					26.3.2.3.2.4 Diencephalic/hypothalamic neurohormones and neuropeptides
	26.4 Adult neurogenesis and plasticity
		26.4.1 Anatomy of adult neurogenesis
			26.4.1.1 Neurogenesis domains
			26.4.1.2 Influence of physiological parameters on neurogenic activity
		26.4.2 Molecular and cellular mechanisms of adult neurogenesis
			26.4.2.1 Localization, identity, and properties of adult progenitor cells
				26.4.2.1.1 NSCs in the adult telencephalon: markers and lineages
					26.4.2.1.1.1 Continuous lineages from embryo to adult contribute to generate an ``ordered'' pallial structure
					26.4.2.1.1.2 Changes in neurogenesis with aging
				26.4.2.1.2 NSCs at the adult MHB: markers and lineages
				26.4.2.1.3 NSCs in the adult cerebellum: markers, lineage
			26.4.2.2 Molecular pathways of adult neural progenitor maintenance and recruitment
				26.4.2.2.1 Notch
				26.4.2.2.2 microRNA-9
				26.4.2.2.3 Fezf2
				26.4.2.2.4 Fgf
				26.4.2.2.5 Steroids
				26.4.2.2.6 BDNF
				26.4.2.2.7 Id (inhibitor of DNA binding)
			26.4.2.3 Adult neurogenesis and plasticity upon brain or spinal injury
				26.4.2.3.1 Neurogenesis and regeneration in the telencephalon
				26.4.2.3.2 Neurogenesis and regeneration in the diencephalon (DA neurons)
				26.4.2.3.3 Neurogenesis and regeneration in the optic tectum
				26.4.2.3.4 Neurogenesis and regeneration in the cerebellum
				26.4.2.3.5 Neurogenesis and regeneration in the spinal cord
	References
27 - Gene regulatory networks controlling neuronal development: enhancers, epigenetics, and functional RNA
	27.1 Introduction-genomic control of cell identity in the brain
	27.2 Overview of gene regulation and the control of neuronal diversity
	27.3 Interactions between transcription factors, regulatory DNA, and epigenetics
	27.4 Enhancers
		27.4.1 Mapping and functional prediction of enhancers in the brain
		27.4.2 Enhancer activity in brain development
		27.4.3 Combinatorial enhancer binding of transcription factors activates or represses
		27.4.4 Comparative genomics-evolutionary conservation and novelty of brain enhancers
		27.4.5 Example: ARX expression is regulated by coordinated activity of distal enhancers
		27.4.6 Role of enhancer variation in neurodevelopmental and psychiatric disorders
		27.4.7 Current questions regarding enhancer function
	27.5 Epigenetics
		27.5.1 How chromatin state contributes to gene regulation
		27.5.2 Functional genome annotation
			27.5.2.1 DNA methylation
			27.5.2.2 Histone modification
			27.5.2.3 Chromatin accessibility
		27.5.3 Lineage specification and chromatin in the brain
		27.5.4 Interaction between transcription factors and chromatin
		27.5.5 Role of chromatin remodelers in neurodevelopmental disorders
		27.5.6 Current questions regarding epigenetics
	27.6 Regulatory RNA in brain development
		27.6.1 Functional RNA: miRNA, lncRNA, eRNA
		27.6.2 miRNA: a brief overview
		27.6.3 lncRNA-evidence for function
		27.6.4 eRNA-transcriptional artifacts or functional molecules?
		27.6.5 Current questions regarding functional RNA
	27.7 Putting it all together-gene regulatory networks
		27.7.1 Example: Nkx2-1 in the basal ganglia
	27.8 Conclusion
	References
28 - Posttranscriptional and translational control of neurogenesis: roles for RNA-binding proteins
	28.1 Introduction
		28.1.1 Neurogenesis
		28.1.2 Posttranscriptional regulation
	28.2 Alternative splicing
		28.2.1 Global and dynamic splicing patterns
		28.2.2 Trans-regulators of splicing
		28.2.3 Summary I
	28.3 From nucleus to cytoplasm
		28.3.1 The exon junction complex
		28.3.2 Nonsense-mediated decay
		28.3.3 Summary II
	28.4 Translational control
		28.4.1 Core translational machinery
		28.4.2 The elavl family members
		28.4.3 RNA localization, transport, and translation
		28.4.4 Summary III
	28.5 The epitranscriptome
		28.5.1 Readers and writers
		28.5.2 Summary IV
	28.6 Perspectives
	References
29 - Human neurogenesis: single-cell sequencing and in vitro modeling
	29.1 Introduction
	29.2 Single-cell sequencing modalities
		29.2.1 Whole-cell RNA-sequencing to identify molecular signatures of known and novel cell types
		29.2.2 Nuclei sequencing to discover novel human cell types
		29.2.3 Multimodal integration of transcriptomic, morphologic, and physiologic features highlights functional significance of cellu ...
		29.2.4 ATAC-seq, methylation, and other measures of chromatin state
		29.2.5 Other modalities
		29.2.6 In situ sequencing and other imaging strategies
	29.3 Overview of analytical approaches and strategies
		29.3.1 Clustering and basic analysis strategies
		29.3.2 Approaches to lineage reconstruction
			29.3.2.1 In vitro modeling of human neurogenesis
	29.4 Cell culture strategies
		29.4.1 Stem cells and reprogramming
		29.4.2 Adherent culture systems
		29.4.3 Brain organoid models
	29.5 Modeling development in organoids
		29.5.1 Regionalization
		29.5.2 Timing of maturation compared to normal development
		29.5.3 Developmental trajectories and neuronal differentiation
		29.5.4 Cellular diversity
		29.5.5 Architectonics
		29.5.6 Cellular dynamics and migration
		29.5.7 Reproducibility
	29.6 Regional interactions
		29.6.1 Whole brain organoids
		29.6.2 Organoid fusing
	29.7 Functional activity
		29.7.1 Modeling circuits
		29.7.2 Single-cell analysis of in vitro cerebral organoid models
		29.7.3 Organoid models to study human evolution
	29.8 Disease phenotypes
	29.9 Engineering organoids
	29.10 Conclusion
	References
Part III: Development of glia, blood vessels, choroid plexus, immune cells in the nervous system
30 - A golden age for glial biology
	30.1 Overview
	30.2 Brief summary of section chapters
		30.2.1 Chapters 31-33: neural stem cells and astrocytes
		30.2.2 Chapters 34-40: myelinating cells
		30.2.3 Chapters 41-43: microglia, ependyma, perivascular cells, and meninges
	30.3 Conclusion
31 - Neural stem cells among glia
	31.1 Introduction
	31.2 NSCs among glia in the developing brain
		31.2.1 Neuroepithelial cells
		31.2.2 Radial glia
		31.2.3 Intermediate (basal) progenitor cells
		31.2.4 Outer radial glia
	31.3 Molecular regulation of progenitor proliferation, cell fate, and polarity
		31.3.1 Mapping progenitor cell fates
		31.3.2 Role of apical-basal polarity in progenitors
			31.3.2.1 Regulation at the apical surface
			31.3.2.2 Role of the basal process
		31.3.3 New models of molecular regulation in progenitors
	31.4 NSCs among glia in the postnatal brain
		31.4.1 RG persist after birth and function as NSCs in some vertebrates
		31.4.2 NSCs (Type B1 cells) in the adult mammalian V-SVZ
		31.4.3 NSCs (radial astrocytes) in the adult hippocampus
		31.4.4 Regulation of adult NSCs
	31.5 Link between embryonic and adult glial cells that function as NSCs
	31.6 Origin of oligodendrocytes from RG and adult V-SVZ astrocytes
	31.7 Evolutionary perspective
	31.8 Perspective for brain repair
	31.9 Conclusion
	Acknowledgments
	References
32 - Mechanisms of astrocyte development
	32.1 Introduction
		32.1.1 Overview of astrocyte function in the central nervous system
		32.1.2 Why is the study of astrocytes uniquely challenging?
			32.1.2.1 Interspecies differences in astrocyte developmental lineages
			32.1.2.2 The absence of a clear developmental endpoint
			32.1.2.3 The lack of molecular tools
		32.1.3 Overview of the chapter
	32.2 The origins of astrocytes
		32.2.1 Use of in vitro culture methods to generate astrocytes
		32.2.2 Use of induced pluripotent stem cell technology to generate astrocytes in vitro
		32.2.3 Molecular mechanisms of astrocyte specification and initiation
			32.2.3.1 1996-99: Role of signaling molecules
			32.2.3.2 1996-99: Suppression of astrocyte fate and epigenetic states
			32.2.3.3 2000-04: Discovery of the role of Notch signaling to promote astrocytes
			32.2.3.4 2005: Feedback mechanisms controlling astrocyte fate
			32.2.3.5 2006: Discovery of NFIA, which controls the neuron-glia switch
				32.2.3.5.1 2009: NFIA also promotes differentiation of astrocytes, after the neuron-glia switch
				32.2.3.5.2 2012: Relationship of NFIA with transcription factor Sox9
				32.2.3.5.3 2014: Relationship of NFIA with transcription factors Sox10 and Olig2 to control oligodendrocyte fate
			32.2.3.6 2006-present: discoveries of other pathways, transcription factors, and mechanisms of astrocyte fate determination
				32.2.3.6.1 Receptors and signaling pathways: ErbB4 and MEK/ERK pathway
				32.2.3.6.2 Transcription factors: Coup-TFI, Lhx2, and Zbtb20
				32.2.3.6.3 Epigenetic controls: Hdac3 in the astrocyte-oligodendrocyte fate decision and the role of chromatin loops
		32.2.4 Patterning of the neural tube and astrocytes
			32.2.4.1 Are astrocytes patterned?
			32.2.4.2 Patterning as a mechanism to generate astrocyte diversity
	32.3 Mechanisms of astrocyte differentiation
		32.3.1 The search for stage-specific and subtype-specific pan-astrocytic markers
			32.3.1.1 Classical markers of astrocytes
			32.3.1.2 Newly identified transcription factors as astrocyte markers
			32.3.1.3 Functional proteins as mature astrocyte markers
			32.3.1.4 Emerging astrocyte markers based on transcriptional profiling
		32.3.2 Defining the intermediate phases of astrocyte lineage trajectory
			32.3.2.1 Directionality of astrocyte migration from the subventricular zone
			32.3.2.2 Location of astrocyte precursor proliferation
			32.3.2.3 Molecular regulation of the intermediate phases of astrocyte development
	32.4 Morphologic and functional maturation of astrocytes
		32.4.1 Morphologic maturation of astrocytes
		32.4.2 Functional maturation of astrocytes
			32.4.2.1 Lessons from the fly about neuron-glia interactions
			32.4.2.2 Neuronal activity sculpts astrocyte maturation
	32.5 The development of astrocyte diversity
		32.5.1 Morphological diversity across the adult central nervous system
		32.5.2 Regional and functional diversity across the adult central nervous system
		32.5.3 Does regional diversity control function of spatially separated astrocytes?
		32.5.4 Local diversity at specific regions and their contribution to astrocyte function
		32.5.5 Other aspects of astrocyte diversity
	32.6 Conclusions and future directions
	References
33 - Astrocyte-neuron interactions in synaptic development
	33.1 Developmental stages of synapse formation and maturation
	33.2 Role of astrocytes in synaptic development
		33.2.1 Contact-mediated astrocyte synaptogenic signals
			33.2.1.1 Integrin-protein kinase C
			33.2.1.2 Neurexin
			33.2.1.3 Gamma protocadherins
			33.2.1.4 Neuroligins
			33.2.1.5 Eph/ephrin
		33.2.2 Astrocyte-secreted synapse-regulating signals
			33.2.2.1 Synapse number
				33.2.2.1.1 Thrombospondin
				33.2.2.1.2 Sparcl1
				33.2.2.1.3 Transforming growth factor beta
			33.2.2.2 Presynaptic function
				33.2.2.2.1 Cholesterol and lipid metabolism
			33.2.2.3 Postsynaptic function
				33.2.2.3.1 Glypicans
			33.2.2.4 Tumor necrosis factor alpha
				33.2.2.4.1 Chordin-like 1
				33.2.2.4.2 Chondroitin sulfate proteoglycans
			33.2.2.5 Negative synaptic regulators
				33.2.2.5.1 SPARC
			33.2.2.6 Additional astrocyte-derived signals
			33.2.2.7 Inhibitory synapses
		33.2.3 Astrocyte elimination of synapses
	33.3 Region, temporal, and neuronal regulation of astrocyte synaptogenic cues
		33.3.1 Regional heterogeneity of astrocyte synaptogenic gene expression
		33.3.2 Temporal changes in astrocyte synaptogenic gene expression
		33.3.3 Neuronal regulation of synaptogenic cue expression in astrocytes
	33.4 Conclusion
	References
34 - Specification of oligodendrocytes
	34.1 Introduction
	34.2 Determinants of oligodendroglial fate
	34.3 Determinants of oligodendroglial identity
	34.4 Determinants of progenitor state maintenance
	34.5 Determinants of progression from the progenitor state
	34.6 Determinants of terminal differentiation and the fully differentiated state
	34.7 Concluding remarks perspectives
	References
35 - Signaling pathways that regulate glial development and early migration-oligodendrocytes
	35.1 Introduction
	35.2 Signaling pathways regulating the initial appearance of oligodendrocyte precursors
		35.2.1 Timing and localization of appearance of OPCs
		35.2.2 Molecular control of early OPC appearance
			35.2.2.1 Sonic hedgehog
			35.2.2.2 Bone morphogenetic proteins
			35.2.2.3 Wnts
			35.2.2.4 Neuregulin
			35.2.2.5 FGF
	35.3 Regulation of OPC migration
		35.3.1 Mechanisms of OPC dispersal: engagement of the vasculature
		35.3.2 Molecular guidance of OPC dispersal
			35.3.2.1 Netrins
			35.3.2.2 Semaphorins
		35.3.3 Molecular control of OPC motility
			35.3.3.1 Growth factors
			35.3.3.2 Neurotransmitters and channels
			35.3.3.3 Chemokines
		35.3.4 Signals regulating the final localization of oligodendrocytes
			35.3.4.1 CXCL1
			35.3.4.2 Tenascin C
	35.4 Regulation of OPC differentiation
		35.4.1 Cell extrinsic regulation of oligodendrocyte differentiation
			35.4.1.1 LINGO-1
			35.4.1.2 PSA-NCAM
			35.4.1.3 Notch/delta
		35.4.2 Cell-intrinsic regulators of oligodendrocyte differentiation
		35.4.3 Transcriptional regulators of OPC terminal differentiation
			35.4.3.1 Negative transcriptional regulators of OPC terminal differentiation
			35.4.3.2 Positive regulators of OPC terminal differentiation
			35.4.3.3 Intrinsic transcriptional regulation of oligodendrocyte maturation and myelination
	35.5 Epigenetic regulation of oligodendrocyte development
		35.5.1 ATP-dependent chromatin remodelers
		35.5.2 Histone-modifying enzymes
		35.5.3 miRNAs in oligodendrocyte development
		35.5.4 lncRNAs in oligodendrocyte development
	35.6 Conclusions
	References
36 - Neuron-glial interactions and neurotransmitter signaling to cells of the oligodendrocyte lineage
	36.1 Introduction
	36.2 Distinguishing characteristics of OPCs, premyelinating oligodendrocytes, and mature oligodendrocytes
		36.2.1 OPC distribution, morphology, and proliferation
		36.2.2 Distribution and morphology of premyelinating oligodendrocytes and oligodendrocytes
		36.2.3 Physiological properties of oligodendrocyte lineage cells
		36.2.4 Transcriptional expression profiles across the oligodendrocyte lineage
	36.3 Neurotransmitter signaling within the oligodendrocyte lineage: glutamate
		36.3.1 AMPA receptor signaling within oligodendrocyte lineage cells
		36.3.2 NMDA receptor signaling within oligodendrocyte lineage cells
		36.3.3 Metabotropic glutamate receptors within oligodendrocyte lineage cells
		36.3.4 Glutamate receptor expression during progenitor differentiation
	36.4 Neurotransmitter signaling within the oligodendrocyte lineage: GABA, acetylcholine, and ATP
	36.5 Synaptic signaling between neurons and OPCs
		36.5.1 A surprising discovery: evidence for the existence of neuron-OPC synapses
		36.5.2 Do neuron-OPC synapses regulate oligodendrogenesis?
		36.5.3 Activity-dependent myelination
		36.5.4 Additional features of neuron-OPC synapses: signaling functions beyond oligodendrogenesis?
	36.6 Oligodendrocyte lineage cells in the context of disease and injury
		36.6.1 OPC reactivity and vulnerability of oligodendrocyte lineage cells to pathology
		36.6.2 Perinatal hypoxia and ischemia
		36.6.3 OPCs and hypomyelination/demyelination
		36.6.4 Tumorigenesis and gliomas
	36.7 Conclusions/future directions
	References
37 - Nonmammalian model systems of zebrafish
	37.1 History and attributes of the zebrafish model system
		37.1.1 Establishment of a new animal model
		37.1.2 The zebrafish toolbox
	37.2 Zebrafish glial classification
	37.3 Zebrafish oligodendrocyte development
		37.3.1 Oligodendrocyte specification
		37.3.2 Oligodendrocyte lineage cell migration, proliferation, and differentiation
	37.4 Zebrafish peripheral glia
		37.4.1 Schwann cells and the zebrafish lateral line system
		37.4.2 Genetic control of peripheral glial development
		37.4.3 Motor root perineurial cells originate as CNS glia
		37.4.4 Glial cell interactions at the CNS-PNS interface
	37.5 Zebrafish radial glia
	37.6 Zebrafish microglia
	37.7 Conclusion
	References
38 - Specification of macroglia by transcription factors: Schwann cells
	38.1 Introduction
	38.2 Specification of Schwann cells from neural crest
		38.2.1 Alternate developmental fates of Schwann cell precursors
	38.3 Immature Schwann cells: radial sorting and transition to myelination
	38.4 Signaling pathways regulating the myelin program
		38.4.1 Neuregulin
		38.4.2 G protein-coupled receptor 126 signaling
		38.4.3 Mitogen-activated protein kinase signaling. ERK1/2
		38.4.4 PI-3 kinase and mTOR signaling
		38.4.5 Calcium and prostaglandin signaling converging on nuclear factor of activated T-cell (NFAT) transcription factors in Schwan ...
		38.4.6 Negative regulators of myelination
	38.5 Integration of signaling pathways at myelin genes
	38.6 Epigenetic regulation of Schwann cell differentiation
	38.7 Reprogramming Schwann cell behavior in pathology
	38.8 Conclusion
	List of acronyms and abbreviations
	References
39 - Signaling pathways that regulate glial development and early migration-Schwann cells
	39.1 Introduction
	39.1 Overview of Schwann cell development
		39.1.1 Schwann cell precursors, the glial cells of early embryonic nerves
		39.1.2 Immature Schwann cells
		39.1.3 Axonal signals
		39.1.4 Boundary cap cells
	39.2 Developmental potential and Schwann cell plasticity
	39.3 Major differences among migrating neural crest cells, SCP, and iSch
	39.4 Gliogenesis from crest cells: the appearance of SCP
		39.4.1 HDAC1/2
		39.4.2 Sox10
		39.4.3 NRG1
		39.4.4 Notch
	39.5 NRG1 and Notch signaling IN SCP
		39.5.1 Survival
		39.5.2 Migration
		39.5.3 NRG1 on developing axons
		39.5.4 NRG1 and Notch interact to promote SCP survival and iSch generation
	39.6 Schwann cell generation and the architectural reorganization of peripheral nerves
	39.7 SCP and early Schwann cells control neuronal survival, nerve fasciculation, and synapse formation
		39.7.1 Neuronal survival
		39.7.2 Fasciculation and synapse formation
	39.8 Schwann cells in late embryonic and perinatal nerves
	39.9 Signals that drive Schwann cell proliferation in vivo
		39.9.1 Notch
		39.9.2 TGFβ
		39.9.3 YAP/TAZ pathway
		39.9.4 NRG1
		39.9.5 Laminin and GPR126
	39.10 Signals that promote Schwann cell death and survival in vivo
	39.11 Radial sorting
		39.11.1 Laminin and integrins
		39.11.2 NRG1
		39.11.3 Lgi4
		39.11.4 GPR126
		39.11.5 Sox10
		39.11.6 HDAC1/2
		39.11.7 Zeb2
		39.11.8 The HIPPO pathway
		39.11.9 Jab 1
		39.11.10 Wnt/beta-catenin signaling
	39.12 The onset of myelination
		39.12.1 Positive regulators
		39.12.2 The onset of myelination: negative regulators
	39.13 Conclusions
	Acknowledgments
	References
40 - Structure and function of myelinated axons
	40.1 Introduction
	40.2 Evolution of the myelinated axon
		40.2.1 Ion channel clustering in the axon
		40.2.2 Myelin-enabling ``wrap-id'' advances in cognition
	40.3 Myelinating glial cells and axoglial interactions
	40.4 Nodes of Ranvier: structure, composition, and function
		40.4.1 Nodes of Ranvier
		40.4.2 Paranodal junctions
		40.4.3 Juxtaparanodes
	40.5 Assembly of nodes of Ranvier
		40.5.1 Clustering of Na+ channels at nodes of Ranvier in the PNS
		40.5.2 Clustering of Na+ channels at nodes of Ranvier in the CNS
	40.6 Long-term maintenance of nodes in the PNS and CNS
	40.7 Function of nodes in AP propagation and initiation
		40.7.1 Developmental maturation of Na+ channel complexes at nodes of Ranvier
		40.7.2 Nodal spacing contributes to neuronal computations
		40.7.3 Proximal nodes of Ranvier in determining neuronal firing patterns
	40.8 Nodes of Ranvier in nervous system disease and injury
		40.8.1 Autoimmune disorders
		40.8.2 Developmental neuropsychiatric disorders
	40.9 Conclusions and outlook
	References
41 - Microglia
	41.1 Introduction
	41.2 Origin and maintenance of microglia
		41.2.1 Developmental origins of microglia
		41.2.2 Microglia in different species
		41.2.3 Microglia turnover in the adult brain
	41.3 Microglia as dynamic cells in the CNS
		41.3.1 Challenging the term ``resting'' microglia in the healthy CNS
		41.3.2 Microglial responses to localized trauma in vivo
	41.4 Microglial activation
	41.5 Microglial interactions with other cell types
	41.6 Microglia and disease
		41.6.1 Microglia in multiple sclerosis
		41.6.2 Microglia in stroke
		41.6.3 Microglia in Alzheimer's disease
		41.6.4 Microglia in neuropathic pain
		41.6.5 Single-cell approaches to understand microglia heterogeneity
	41.7 Concluding remarks
	List of abbreviations
	References
42 - Ependyma
	42.1 Introduction
	42.2 Structure of cells in contact with the ventricles
		42.2.1 Structure of multiciliated ependymal cells
			42.2.1.1 Structure of tanycytes
			42.2.1.2 Structure of other cells in contact with ventricles
		42.2.2 Origin and developmental mechanisms
			42.2.2.1 Ependymal cell specification
			42.2.2.2 Ependymal cell differentiation
			42.2.2.3 Ependymal cell maturation
		42.2.3 Functions in the brain
			42.2.3.1 Ependymal epithelium: interface between brain and CSF
				42.2.3.1.1 The ependymal junctions
				42.2.3.1.2 A filter for brain-CSF exchange
				42.2.3.1.3 A regulator of osmotic pressure
				42.2.3.1.4 A barrier against harmful substances
				42.2.3.1.5 A regulator of peptide concentrations
			42.2.3.2 Trophic and metabolic support by ependymal cells
			42.2.3.3 Can ependymal cells function as neural stem cells?
		42.2.4 Associated pathologies
			42.2.4.1 Ependymoma
			42.2.4.2 Hydrocephalus
	42.3 Summary
	References
43 - Meninges and vasculature
	43.1 Meninges in development
		43.1.1 Meninges assembly to adult structure: histology and molecular signaling
			43.1.1.1 Emergence and maturation of the meningeal fibroblast layers
			43.1.1.2 Developmental timeline and function of nonfibroblast cells of the meninges
		43.1.2 Meninges-brain interface: signals from the meninges regulate development of the CNS
			43.1.2.1 Meningeal Cxcl12 in fore- and hindbrain development
			43.1.2.2 Meningeal retinoic acid in forebrain and hindbrain development
			43.1.2.3 Meningeal bone morphogenic proteins in forebrain development
			43.1.2.4 Meningeal deposition and maintenance of the pial BM
		43.1.3 Perspectives on the meninges as an interface between the immune system and the brain
	43.2 Development of the CNS vasculature
		43.2.1 Timing and molecular mechanisms of CNS angiogenesis
			43.2.1.1 Developmental timing of CNS vascularization
			43.2.1.2 VEGF ligands regulate CNS vascular growth and patterning
			43.2.1.3 Endothelial Wnt-β-catenin signaling is CNS vascular development
			43.2.1.4 Integrin αvβ8 in CNS vascular development
			43.2.1.5 Retinoic acid in cerebrovascular development
		43.2.2 Establishment of the BBB
			43.2.2.1 Developmental timing of BBB emergence
			43.2.2.2 Molecular control of BBB development
			43.2.2.3 Mural cells in regulation of vascular development and BBB maturation
		43.2.3 Vascular contribution to neurodevelopmental events
			43.2.3.1 Vascular regulation of neuro- and oligodendrogenesis
			43.2.3.2 The embryonic vasculature as a migratory scaffold in the forebrain
			43.2.3.3 The brain vasculature shapes axonal architecture
		43.2.4 hiPSC-based BBB culture models: lessons from CNS vascular development
		43.2.5 Summary and conclusions
	References
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W
	X
	Y
	Z
Back Cover