Front Cover -- Comprehensive Developmental Neuroscience: Cellular Migration and Formation of Neuronal Connections -- Copyright -- Editors-in-Chief -- Section Editors -- Contents -- Contributors -- Introduction to Comprehensive Developmental Neuroscience -- Section I: Formation of Axons and Dendrites -- Chapter 1: Development of Neuronal Polarity In Vivo -- 1.1. Introduction -- 1.2. Axon Initiation In Vitro Versus In Vivo -- 1.2.1. Axon Initiation In Vitro -- 1.2.2. Axon Initiation In Vivo -- 1.3. Distinction Between Cues Regulating Axon Specification Versus Axon Growth -- 1.4. Extracellular Cues Regulating Neuronal Polarization and Axon Initiation -- 1.4.1. Netrin-1 and Wnt Control Axon Initiation in C. elegans -- 1.4.2. Polarized Emergence of the Axon in Retinal Ganglion Cells of Xenopus -- 1.4.3. Extracellular Cues Underlying the Emergence of Axon and Dendrites in Mammalian Neurons -- 1.5. Intracellular Pathways Underlying Neuronal Polarization -- 1.5.1. Role of Local Protein Translation and Degradation for Axon Specification and Axon Growth -- 1.5.2. Role of Cytoskeletal Dynamics in Axon Initiation and Growth -- 1.5.3. Major Signaling Pathways Involved in Axon Initiation and Growth -- 1.5.3.1. LKB1 and its Downstream Kinases SAD-A/B and MARK1-4 -- 1.5.3.2. PAR3-PAR6-APKC -- 1.5.3.3. Ras- and Rho-Family of Small GTPases -- 1.5.3.4. PI3-Kinase and PTEN Signaling during Axon Specification -- 1.5.3.5. AKT/Protein Kinase B -- 1.5.3.6. GSK3 and Axon Specification -- References -- Chapter 2: Role of the Cytoskeleton and Membrane Trafficking in Axon-Dendrite Morphogenesis -- 2.1. Introduction -- 2.2. Developmental Stages -- 2.3. Role of Cytoskeleton in Establishment of Neuronal Polarity -- 2.3.1. Actin -- 2.3.2. Actin Dynamics During Axon Formation -- 2.3.3. Microtubules -- 2.3.4. Microtubules Dynamics During Axon Formation.

2.3.5. Cytoskeletal Dynamics During Dendritic Growth and Arborization -- 2.3.6. Subcellular Cytoskeletal Specializations -- 2.4. The Role of (Membrane) Trafficking During Neuronal Polarization -- 2.4.1. Trafficking During Early Neuronal Development -- 2.4.2. Motor Protein-Based Transport in Axons and Dendrites -- 2.4.3. The Secretory and Endosomal Pathway -- 2.4.4. RNA Transport and Local Translation -- 2.4.5. Barriers for the Segregation of Functional Domains -- 2.4.6. Protein Stabilization and Degradation -- 2.5. Maintaining Neuronal Polarity -- 2.6. Future Work on Neuronal Morphogenesis -- References -- Chapter 3: Axon Growth and Branching -- 3.1. Introduction -- 3.2. Cell Biological Mechanisms -- 3.2.1. Growth Cones: Structure and Function -- 3.2.2. Regulation of Cytoskeleton Assembly in Growth Cones and Axons -- 3.2.2.1. Actin -- 3.2.2.2. Microtubules -- 3.2.3. Cell Adhesion and the Clutch Model -- 3.2.4. Membrane Trafficking and Axonal Transport -- 3.2.5. Local Translation: An Emerging Role in Axon Growth and Branching -- 3.2.6. Cell Size Control -- 3.3. Extracellular Regulation During Development -- 3.3.1. NGF and Neurotrophic Factors -- 3.3.2. Guidance Molecules: Netrin, Slit, Semaphorin, Ephrin, and Wnt -- 3.3.3. Cell Adhesion Molecules: Permissive or Instructive -- 3.3.4. Myelin-Derived Inhibitors: Nogo, Myelin-Associated Glycoprotein, and Oligodendrocyte-Myelin Glycoprotein -- 3.3.5. Neural Activities: Influence on Axon Growth and Branching Stability -- 3.3.6. Other Molecules -- 3.4. Intracellular Signaling Mechanisms -- 3.4.1. The Rho Family Small GTPases: Linking Receptors to the Cytoskeleton -- 3.4.2. Calcium -- 3.4.3. Cyclic Nucleotides as Second Messengers and Modulators -- 3.5. Concluding Remarks -- References -- Chapter 4: Axon Guidance: Semaphorin/Neuropilin/Plexin Signaling -- 4.1. Introduction: General Features of Axon Guidance.

4.2. Discovery of the Semaphorin, Neuropilin, and Plexin Families -- 4.3. The Class 3 Secreted Semaphorins in Vertebrates: Neuropilin/Plexin Receptors and Signal Transduction Cascades -- 4.3.1. Class 3 Semaphorin Receptors -- 4.3.2. Signaling Downstream of Sema3 Receptors -- 4.3.2.1. Receptor Activation -- 4.3.2.2. Signaling for Modulation of Adhesion Sites -- 4.3.2.3. Signaling for Cytoskeleton Remodeling -- 4.3.2.4. Attractive Sema3 Signaling -- 4.3.3. Dynamics of the Sema3 Receptor Complex -- 4.4. Generating Diversity of Axon Responses to Sema3's -- 4.4.1. Modulators of Semaphorin Signaling -- 4.4.2. Posttranscriptional Mechanisms Regulating the Sema3 Signaling -- 4.4.2.1. Proteolytic Cleavage -- 4.4.2.1.1. Processing Sema3's -- 4.4.2.1.2. Processing Sema3 receptors -- 4.4.2.2. Endocytosis and Local Trafficking of the Receptors -- 4.4.2.3. Modulation of Second Messenger and Signaling Molecules Downstream of Class 3 Semaphorin -- 4.4.2.3.1. Control by cyclic nucleotide levels -- 4.4.2.4. Conclusion -- 4.5. Uncovering the in vivo Contribution of Sema3's to Axon Guidance: Insights from Animal Models -- 4.6. Sema3 Signaling and Sensorimotor Projections -- 4.6.1. Sema3's Control Motor Axons Navigation -- 4.6.2. Sema3's Regulate Sensory Axon Navigation and Connectivity -- 4.7. Sema3 Signaling and Connections of the Cerebral Cortex -- References -- Chapter 5: Roles of Eph-Ephrin Signaling in Axon Guidance -- 5.1. Introduction -- 5.1.1. Structure, Nomenclature, and Evolution of Eph Receptors and Ephrins -- 5.2. Eph-Ephrin Signaling Is Essential for Axon Guidance in Many Contexts -- 5.2.1. Eph-Ephrin Signaling Is Used by Some Axons to Cross/Not Cross the Midline -- 5.2.2. Reciprocity of Eph-Ephrin Signaling at a Motor Neuron Choice Point -- 5.2.3. Gradients of Ephrin-As Expressed in Intermediate Targets Can Sort Axons.

5.2.4. Ephs and Ephrins Are Required for Topographic Mapping -- 5.2.5. Ephrin-Mediated Guidance in the Olfactory System -- 5.2.6. In Vitro Assays of Eph Signaling in Axon Guidance -- 5.3. Modes of Eph-Ephrin Signaling in Axon Guidance -- 5.3.1. Forward Signaling -- 5.3.2. Ephrin-B Reverse Signaling -- 5.3.3. Ephrin-A Reverse Signaling -- 5.3.4. Cis versus Trans Signaling -- 5.4. Eph-Ephrin Signaling in Invertebrate Nervous Systems -- 5.4.1. Drosophila: Axon Branching -- 5.4.2. Manduca: Interaxonal Sorting and Midline Neuronal Migrations -- 5.4.3. C. elegans: Midline Crossing, Responses to Hypoxia, and Regeneration -- 5.5. Eph Signaling in Axon Regeneration -- Acknowledgments -- References -- Chapter 6: Axon Guidance: Slit-Robo Signaling -- 6.1. Introduction -- 6.2. Slits and Their Receptors -- 6.2.1. Slit Discovery and Structure -- 6.2.2. Identification of the Slit Receptor Robo -- 6.2.3. Slit and Robo Interactions -- 6.3. Slit-Robo Function in Midline Crossing -- 6.3.1. Spatial Regulation of Slit and Robo Expression -- 6.3.2. Posttranscriptional Robo Regulation -- 6.3.3. Regulation of Robo Protein Expression at the Midline -- 6.3.3.1. Drosophila and Vertebrate Midlines -- 6.3.3.2. C. elegans Midline -- 6.3.4. Regulation of Robo Signaling at the Midline in Vertebrates -- 6.3.5. Slit-Robo Signaling for Exiting the Midline -- 6.4. Modulation of Slit-Robo Signaling -- 6.4.1. Transcriptional Control -- 6.4.2. Regulation of Slit-Robo Signaling by Metalloprotease Cleavage -- 6.4.3. Regulation of Slit-Robo Signaling by Ubiquitination -- 6.5. Signaling Downstream of Robo -- 6.5.1. Rho Family of Small GTPases -- 6.5.2. Abelson Tyrosine Kinase -- 6.6. Beyond the Midline: Additional Roles for Slit-Robo in the Nervous System -- 6.6.1. Lateral Positioning -- 6.6.2. Cell Migration and Cell Polarity -- 6.6.3. Dendritic and Axonal Outgrowth and Branching.

6.7. Slit-Robo Contributions to Axon Targeting in a Complex Target Field -- 6.8. Involvement of Slit-Robo in Disorders of the Nervous System -- 6.9. Slit-Robo: Players Outside the Nervous System -- 6.9.1. Organogenesis -- 6.9.2. Slits in Cell Migration and Adhesion -- 6.9.3. Slits in Vascular Patterning -- 6.10. Conclusion -- References -- Chapter 7: Nonconventional Axon Guidance Cues -- 7.1. Introduction -- 7.2. Morphogens -- 7.2.1. The Hedgehog Family -- 7.2.2. The TGF-β Superfamily -- 7.2.3. The Wnt/Wingless Family -- 7.3. Morphogens in Axon Guidance -- 7.3.1. The Roles of Shh in Axon Guidance -- 7.3.1.1. Shh is a Chemoattractant for Commissural Axons -- 7.3.1.2. Boc is a Receptor for Shh in the Guidance of Commissural Axons to the Floor Plate -- 7.3.1.3. Shh Functions through a Novel, Noncanonical Src-Family-Kinase-Dependent Signaling Pathway in Commissural Axon Gu ... -- 7.3.1.4. Shh Guides Commissural Axons along the Longitudinal Axis of the Spinal Cord -- 7.3.1.5. Shh Induces the Response of Commissural Axons to Semaphorin Repulsion during Midline Crossing -- 7.3.1.6. Shh Signaling is a Negative Regulator of RGC Axon Growth and Functions as a Chemorepellent for RGC Axon Guidance -- 7.3.1.7. Shh is a Chemoattractant for Midbrain Dopaminergic Axons -- 7.3.2. The Roles of TGF-β Superfamily Members in Axon Guidance -- 7.3.2.1. BMPs are Chemorepellents for Commissural Axons -- 7.3.2.2. Dawdle, a Divergent Activin-like TGF-β Family Member, Regulates Motor Axon Pathfinding in Drosophila -- 7.3.2.3. The TGF-β Family Member Unc-129 is Required for Motor Axon Guidance -- 7.3.3. The Roles of Wingless/Wnts in Axon Guidance -- 7.3.3.1. Wnt5 Repels Commissural Axons from the Posterior Commissure -- 7.3.3.2. Wnt4 Controls the A-P Guidance of Ascending Commissural Axons -- 7.3.3.3. Wnts Repel Corticospinal Tract Axons Down the Spinal Cord.

7.3.3.4. Wnt/Ryk and Ca2 are Involved in Axon Guidance in the Corpus Callosum.