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Introduction . ..... ........ .. ..... ...... . ................. -........ .......... .......... 11 Primary Germ Layers and Neural Crest Cell Lineages ............................................. 2 Neural Crest and the Cranial Bauplan ..................... ............................ .............. 4 Topology and Homology along the Neural Crest-Mesoderm Interface ................ ... 10 Neural Crest and the Origins of Craniofacial Pattern .............................................. 14 Conclusion ..1....7.......................... . ............................................... ..... 7 2. NEURAL CREST INDUCING SIGNALS ........................ ... .................. 24 iMarin L. Basch and Marianne Bronner-Fraser Introduction .. ............... . .. ...... ...... ......... ......... ......... ..... ................... ........ 24 Signals from the Ectoderm .............. .. ........................................ ........................... 25 Signals from the :Mesoderm ... ... ..... .. ........ .... ..... .... ..... ... 25 BMPs ....... .... .. . ........... ......... .......... ........................ ............... ........... ...... 25 Writs .........................2.......... .. ..... .... ......... ...... ................. .................. ... 27 FGFs ............ .. ......... ..... ............... . ... .. .. ............... .......... .. .. ................. 28 Notch ................ ........ .. ...... ................ ..................... ........ ............................... 28 Neural Crest induction Is a Multistep Process ......... ... ....................... ..... 29 Conclusions ...........2........................... ....... ... ............................... ............................... 29 3. TRANSCRIPTIONAL REGULATION AT THE NEURAL PLATE BORDER ......... .... ................................................ ........... 32 Thomas D. Sargent Introduction ..... .... ............ ..................... 3.......... ....................................... 32 Dix and Msx Genes .......... . . . ............... ....... . .............................................. 33 TFAP 2 ........ .................. .. . ......... ...... . ............. ....... ...............................38 NC Regulatory Pathways Problems and Prospects ................................................... 41 4. NELRAL CREST DELAMINATION AND MIGRATION: INTEGRATING REGULATIONS OF CELL INTERACTIONS, LOCOMOTION, SURVIVAL AND FATE ....... 45 Jean-L oup Duband Introduction ................................. .4... ............... ........ . ... ......... .. ................... .. ..... 45 Neural Crest Delamination: Their Declaration of Independence ....... ...................... 46 Neural Crest Migration: How to Survive, Move and Develop in a Hostile Environment ..... ........... ....................6.................................................... 64 Conclusion ... ................................... ... .......................................................... .............. 71 5. NEURAL CREST CELL PLASTICITY: SIZE MATTERS .................. 78 Lisa L. Sandell and Paul A. Trainor Introduction ......................................... ... . .................. ....... ............................................ 78 Hindbrain, Hox Genes and Axial Identity ................................................................... 80 Environment Influences Neural Crest/Neural Crest Influences Environment ............ 81 Neural Crest Plasticity Is influenced by Graft Size and Developmental Age ....... ......82 Plasticity in Neural Crest Cell M igration ...................................................................... 85 Neural Crest Cells Direct Species-Specific Craniofacial Morphology ......................... 86 Patterning of the Head and Face by Non-Neural Crest Tissues .................................... 88 Molecular Pathways Involved in Neural Crest Signaling ............................................ 88 Reciprocal In teractions ....................... . ......................................-... ............................ 89 Conclusions ....... ................................................................................................. ........... 90 6. THE CONTRIBUTION OF THE NEURAL CREST TO THE VERTEBRATE BODY ............e................................... 96 Elisabeth Dupin, Sophie Creuzet and Nicole M. Le Douarin Introduction ................... .................................................. ........................................... 96 The Derivatives of the NC .......... ........................................ ........................................... 97 Pathways and Molecular Control of NCC Migration ..... ............................................... 98 The Mesectoderm Is at the Origin of Most Head Structures ..1.................................. 101 The Posterior Limit of the NC-Derived Skeleton in Mammals ................................... 103 Contribution of the nMesectoderm to the Cardiovascular and Periocular Structures ................1................. ......................................... ..... 103 Hox Gene Expression in the Cephalie NCCs and Their Derivatives .0.. .................... 105 Shifting Rostrally the Limit of Hox Gene Expression ................................................ 07 Patterning the Facial Skeleton by the Pharyngeal Endoderm 1........................... .... 107 Role of the Superficial Facial Ectoderm in Shaping the Face ..1 .. .............. ....... 109 Heterogeneity of Progenitors and Stem Cells in the Early NC .......................... 110 Resident NC Stem Cells Are Present in Differentiated Tissues up to Adulthood 1... 11 Plasticity of NC-Derived Phenotypes ............... .... ... ................ ... ...................... 11 oncluding Remarks ................................................................. ........................ .... 113 7. CRANIAL NEURAL CRESIT AND DEVELOPMriENT OF THE HEAD SKELETON ........ .... ................. 120 RobertD . Knight and Thomas F. Schilling Introduction ......... ................................ ....................................................... ........... .... 120 Specification and Migration of the Skeletogenic CNC .......... .................. 120 patterning Influences of Skeletogenic CNC on Surrounding Tissues ......... ....... .... 124 Patterning within Pharyngeal Arch Primordia ...1.....4........... ........... ............... 124 Endoderm Patterns CNC and Is Required for Skeletal Development .................. 126 Pharyngeal Ectoderm Patterns CNC ..... ..................... .......... ................. .. 128 CNC Development and Evolution ............ ...................... .................... .... ... 29 Summary and Conclusions .. .................. ... ..... ......... .. .... ......... 130 8. NEURIAL CREST CONTRIBUTION TO THE CARDIOVASCULAR SYSTEM ...... ......................... 134 Christopher B. Brown and H. Scott Baldwin introduction . ...... ........ ... ..... ................................................. ........ 134 Identification and Characterization of the Cardiac Neural Crest ......................... 136 Cardiac Neural Crest Function in Cardiac Development and Remodeling .........;... 136 Neural Crest Ablation ..... ....... ............................. .... .. ... .. .. 138 Cardiac Neural Crest Function in Pharyngeal Arch Patterning ...... ............ 139 Cardiac Neural Crest in Outflow Tract Septation and Alignment ....................... 139 Myocardial Dysfunction, Elongation, Alignment and the Secondary Heart Field .... 141 Molecular Pathways ... .. . ... ..... ............... ...... .......... 143 Mouse Model of Cardiac Neural Crest Deficiency .. ,. .1.......................... 144 Neurotrophins ........... ............................ ................. ............. 144 Forkhead Transcription Factors FoxC1lFoxC2 ........................................ 144 Tbxl, Fibroblast Growth Factors and DiGeorge Syndrome ........a........... i... . 145 Retinoic A cid ........... ......... __.. ............... .......................... .. .......... ...... ...... 146 Cell-Cell Contact (Connexins) .... ....... ... ........... ......... ...... .................146 Platelet Derived Growth Factor (PDGF) .................... .......... ....... .............. 146 Endothelin ......... .... . ........ ....................... .. . . . 147 TGFP Superfamily Members .......................... ...................... 147 Semaphorins ..... .. ..................... 48 Pitx2 and Laterality .............. ........... .... .. .......... ......... ... 148 Summary 149........ ....... ... . ....._.. ..... ........... .... 149 9. THE GENETIC REGULAFTION OF PIGMENT CELL DEVELOPMENT . ............................................................ 155 Debra L. Silver, Ling Hou and William J Pavan Introduction ............. .......... ..... ....................................... 155 Model Organisms .......... ...... ... ......................... ............ 156 Initial Induction and Expansion of the Pigment Cell Population ....................... ..... 157 Pigment Cell Specification, Differentiation and Survival ............... 159 Pigment Cell Migration and Development: Cell Adhesion and Signaling ................. 161 Concluding Thoughts ........ ......................... ........................ ... 164 10. SPECtIFICATION OF SENSORY NELRON CELL FATE FROM THE NEURAL CREST ...... ........................................... David W. Raible and Josette M. Ungos The Form and Function of Dorsal Root Ganglia Neurons ................................... 1 Neural Crest Origin of the Sensory Ganglia ......... ..................................... Sensory Neuron Cell Types I............. ................ .. ..................................... Specification of Sensory Neurons ..... .. ............ ........................................ Future Challenges ... ..... ........................................................................................ 11. NEURAL CREST AND THE DEVELOPMENT OF THE ENTERIC NERVOUS SYSTEM 18..... .... ..... .......... 18 Richard B. Anderson, Donald F. Newgreen and Heather M. Young The Enteric Nervous System ........................................................................................ 18 O rigins of the E N S ............................. ................................................... ......... .... 18 H irschsprung's D isease ....1.8........................................................ ...... ..... .... 18 Proliferation, Cell Death and Differentiation in the Developing ENS ............. ... 18' Molecules and Signaling Pathways Involved in ENS Development .......................... 18 C onclusions ........................19............ .... . ......................................................... ... . 19 12. GROVWTH FACTORS REGULATING NEURAL CREST CELL FATE DECISIONS ................................................ ..... 19 1,ukas Sommer Plasticity of the N eural Crest ................. ......... .................................. ......... ... ...... 9 Growth Factors Regulating Neural Crest Cell Fates in Culture ............................. 1% Factors Involved in Neural Crest Development in Vivo ...................................... 20C C onclusions ...........................................................................2........................... ......... 203 13. NEURAL CREST STEM CELLS ............................................... ....... 206 Lu Teng and Patricia A. Labosky N eural Crest Stem Cells .......................................................................................... ..... 2906 Identification of Neural Crest Stem Cells (NCSCs) ................................................... 206 Molecular Control of NCSC Differentiation.. ,,....................................................... 208 Postnatal NCSCs, Disease and Cell Therapy ......................................... ............ 210 14. MOLECULAR BASES OF HUMAN NEUROCRISTOPATHIES ...... 213 Heather C. Etchevers, Jeanne Amiel and Stanislas Lyonnet Introduction .... ........................... ............................................................................... 213 Definition of a Neurocristopathy ............................... 2........... .... 214 Clinical Appreciation of Neurocristopathies ...................... ...................................... 214 Gene Cascades Implicated in Human Neurocristopathies . ...................................... 219 Discussion ........ ...... ... ... ........ ... ........ ......... ... .. ....... .... 227 15. EVOLUTION OF THE NEURAL CREST .............................................. 235 Alejandro Barrallo-Gimeno and M. Angela Nieto Introduction: Was There Anything Like This Before? .................................... 235 Neural Crest and the Neural Tube: The Only Way Is Dorsal .................... ..... 236 Cell Migration: A W hole Body to Populate ..... ....... ..... ....... ................................... 237 Consolidation of the Neural Crest Population: The More, the Merrier . ......-....... 238 To Hox or not to Hox ....e... . .. . ...a.. ............ .......... ...... ................; ..... ...... 238 Evolution's Toolbox I. Playing with Genes and Genomes: Two Is Better Than One ... ........ .. . ............. ..... . ... 2...... . l ... . .... .., 239 Evolution's Toolbox 1L Cooption: Take Genes from Your Neighbor Cells ........... 240 Conclusions: So, W hat Now? ................ .. .......... .... .... ......... ... ... 240