This is the first handbook structured according to organ systems to cover both embryogenesis and organ development. It addresses the functions of developmental signaling pathways and growth factors with a focus on cell division, cell migration, and cell differentiation. A uniform article structure throughout the book facilitates easy comparison of data. Applications in molecular medicine are highlighted with chapters on developmental disorders and related novel therapeutic strategies.

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Volume 1.

Preface.

List of Contributors.

Color Plates.

I Cell Signaling and Growth Factors in Development

1 Stem Cells (Christian Paratore and Lukas Sommer).

1.1 Introduction.

1.2 Maintenance of Stemness in Balance with Stem Cell Differentiation.

1.3 The Notch Signaling Pathway.

1.4 Signaling Pathway of the TGFb Family Members.

1.5 Shh Signaling.

1.6 Conclusions.

2 Germ Cells (Pellegrino Rossi, Susanna Dolci, Donatella Farini, and Massimo De Felici).

2.1 Introduction.

2.2 Primordial Germ Cells.

2.3 Oocytes.

2.4 Male Germ Cells.

3 Implantation and Placentation (Susana M. Chuva de Sousa Lopes, Christine L. Mummery, and Sólveig Thorsteinsdóttir).

3.1 Introduction.

3.2 Molecular Mechanisms and Biological Effects.

3.3 Clinical Relevance in Humans.

3.4 Summary.

4 Cell Movements during Early Vertebrate Morphogenesis (Andrea Münsterberg and Grant Wheeler).

4.1 Introduction.

4.2 History: Classic Experiments in the Study of Gastrulation.

4.3 Gastrulation and Neurulation in Different Vertebrate Species.

4.4 Mechanistic Aspects, Molecules and Molecular Networks.

4.5 Conclusion and Outlook.

5 Head Induction (Clemens Kiecker).

5.1 Introduction.

5.2 Classical Concepts for Head Induction.

5.3 Tissues Involved in Anterior Specification.

5.4 Signaling Pathways Involved in Anterior Specification.

5.5 Mechanistic Models for Head Induction.

5.6 Transcriptional Regulators in Anterior Specification.

5.7 Conclusions and Outlook.

6 Anterior-Posterior Patterning of the Hindbrain: Integrating Boundaries and Cell Segregation with Segment Formation and Identity (Angelo Iulianella and Paul A. Trainor).

6.1 Introduction.

6.2 Hindbrain Development.

6.3 Conclusions.

7 Neurogenesis in the Central Nervous System (Véronique Dubreuil, Lilla Farkas, Federico Calegari, Yoichi Kosodo, and Wieland B. Huttner).

7.1 Introduction.

7.2 Intrinsic Regulation of Neurogenesis.

7.3 Extrinsic Regulation of Neurogenesis.

7.4 Cell Cycle Regulation and Neuronal Fate Determination.

7.5 Neuron-generating Asymmetric Cell Division.

7.6 Conclusions.

8 Generating Cell Diversity (Ajay Chitnis).

8.1 Introduction.

8.2 Establishing Early Compartments of the Embryo.

8.3 Early Neurogenesis in the Neural Plate.

8.4 Determination of Neuronal Identities in the Spinal Cord.

8.5 Concluding Remarks.

9 The Molecular Basis of Directional Cell Migration (Hans Georg Mannherz).

9.1 Introduction.

9.2 How and What Moves Cells.

9.3 The Cytoskeleton.

9.4 Motile Membrane Extensions containing Microfilaments.

9.5 Modulation of the Structure of Transient Protusive Membrane Extensions.

9.6 Formation of Substratum Contacts.

9.7 Cell Body Traction.

9.8 Rear Detachment.

9.9 The Role of Microtubules in Cell Migration.

9.10 The Role of Intermediate Filaments in Cell Migration.

9.11 Modulation of the Cytoskeletal Organization by External Signals.

9.12 The Cytoskeletal Organization of Neuronal Growth Cones.

9.13 Conclusions.

10 Cell Death in Organ Development (Kerstin Krieglstein).

10.1 Introduction.

10.2 Programmed Cell Death.

10.3 Genetics of Programmed Cell Death.

10.4 Cell Death Receptors.

10.5 Growth Factor Deprivation.

10.6 Programmed Cell Death in Developing Organs.

10.7 Concluding Remarks.

Volume 2.

II Cell Signaling and Growth Factors in Organogenesis.

11 Dorso-Ventral Patterning of the Vertebrate Central Nervous System (Elisa Martí, Lidia Garc&ıacute;a-Campmany, and Paola Bovolenta).

11.1 Introduction.

11.2 Generating Cell Diversity in the Dorsal Neural Tube.

11.3 Generating Cell Diversity in the Ventral Neural Tube.

11.4 Generation of D-V Patterning in the Anterior Neural Tube Follows Rules Similar to those Used in the Spinal Cord.

11.5 Conclusions and Perspectives.

12 Novel Perspectives in Research on the Neural Crest and its Derivatives (Chaya Kalcheim, Matthias Stanke, Hermann Rohrer, Kristjan Jessen, and Rhona Mirsky).

12.1 General Introduction.

12.2 Novel Techniques to Investigate NC Development and Fate.

12.3 Mechanisms of Specification and Emigration of NC Cells.

12.4 Peripheral Neuronal Lineages: Pluripotentiality and Early Restrictions of Migratory NC.

12.5 Molecular Control of Neuron Development in Peripheral Ganglia.

12.6 Growth Cone Navigation and Innervation of Peripheral Targets.

12.7 Factors Controlling Neuronal Survival in the PNS.

12.8 Glial Cell Development from the NC-Peripheral Glial Lineages: Fate Choice and Early Developmental Events.

12.9 Signals that Control Schwann Cell-precursor Survival and Schwann Cell Generation.

13 Eye Development (Filippo Del Bene and Joachim Wittbrodt).

13.1 Vertebrate Eye Development: An Overview.

13.2 Patterning of the Anterior Neural Plate.

13.3 Transcription Factors Function in the Establishment of Retinal Identity.

13.4 Patterning of the Eye Field and its Medio-lateral Separation.

13.5 Differentiation of Neuroretina and Pigmented Retinal Epithlium.

13.6 Differentiation of Retinal Cell Types.

14 Mammalian Inner Ear Development: Of Mice and Man (Bernd Fritzsch and Kirk Beisel).

14.1 Introduction.

14.2 Morphological and Cellular Events in Mammalian Ear Development.

14.3 Postnatal Maturation.

14.4 Aging, Hair Cell Loss and the Molecular Biology of Hair Cell Regeneration.

15 Limb Development (Susan Mackem).

15.1 Introduction.

15.2 The Major Signaling Pathways in Limb Development.

15.3 Limb Initiation and Formation of the Limb “Organizers”.

15.4 Function of Organizers in Regulating Pattern and Growth along the Limb Axes.

15.5 Coordination of Patterning, Outgrowth and Differentiation: Positive Co-regulation and Feedback Loops Synchronize Output from Limb Organizers, and Antagonism between Signaling Pathways Contributes to Polarity.

15.6 Ongoing Late Regulation and Realization of Pattern.

15.7 Potential Biomedical Applications and Future Directions.

16 Skeletal Development (William A. Horton).

16.1 Introduction.

16.2 Skeletal Morphogenesis.

16.3 Skeletal Growth.

16.4 Therapeutic Considerations.

16.5 Conclusions.

17 Musculature and Growth Factors (Petra Neuhaus, Herbert Neuhaus, and Thomas Braun).

17.1 Introduction.

17.2 Induction of Primary Myogenesis by Cell Signaling and Growth Factors.

17.3 Tour Guides: How Growth Factors Guide Migration of Muscle Precursor Cells During Embryonic Development.

17.4 Control of Muscle Size and Muscle Fiber Diversity by Local and Circulating Growth Factors.

17.5 Growth Factors in Muscle Wasting and Skeletal Muscle Regeneration.

17.6 Does Growth Factor Mediated Recruitment of Uncommitted Stem Cells Contribute to Skeletal Muscle Cell Regeneration?

18 Skin Development (Lydia Sorokin and Leena Bruckner-Tuderman).

18.1 Introduction.

18.2 Morphology of the Skin and Development of Hair Follicles and Other Adnexal Structures.

18.3 Cell Adhesion and the Role of Adhesion Molecules in Development.

18.4 Development of the Dermal Matrix.

18.5 Epithelial-Mesenchymal Interactions and Signaling.

18.6 Epidermal Stem Cells.

18.7 Pathological Skin Conditions Caused by Developmental Abnormalities.

18.8 Future Considerations.

19 Tooth Development (Xiu-Ping Wang and Irma Thesleff).

19.1 Introduction.

19.2 Signaling Pathways and their Networks Regulating Tooth Development.

19.3 Biological Effects.

19.4 Biomedical Application.

19.5 Summary.

20 Gastrointestinal Tract (Daniel Me´nard, Jean-François Beaulieu, François Boudreau, Nathalie Perreault, Nathalie Rivard, and Pierre H. Vachon).

20.1 Introduction.

20.2 Development of the Gastrointestinal Mucosa.

20.3 Gastric Cell Proliferation and Differentiation.

20.4 Intestinal Cell Proliferation and Differentiation.

20.5 Biomedical Applications.

21 Cell Signaling and Growth Factors in Lung Development (David Warburton, Saverio Bellusci, Pierre-Marie Del Moral, Stijn DeLanghe, Vesa Kaartinen, Matt Lee, Denise Tefft, and Wei Shi).

21.1 Introduction.

21.2 Growth Factors and Lung Development.

21.3 Growth Factor Signaling Pathways in Lung Development.

21.4 Regulation of Signaling Networks.

21.5 Developmental Modulation of Growth Factor Signaling by Adapter Proteins.

21.6 Morphogens and Morphogenetic Gradients.

21.7. Conclusion.

22 Molecular Genetics of Liver and Pancreas Development (Tomas Pieler, Fong Cheng Pan, Solomon Afelik, and Yonglong Chen).

22.1 Introduction.

22.2 From the Fertilized Egg to Primitive Endodermal Precursor Cells.

22.3 Commitment to Pancreas and Liver Fates in Xenopus.

22.4 Liver and Pancreas Specification in Mouse, Chicken and Zebrafish.

22.5 Proliferation and Differentiation of Functionally Distinct Pancreatic and Hepatic Cell Populations.

22.6 Transdifferentiation of Pancreas and Liver.

22.7 Pancreas and Liver Regeneration.

22.8 Generation of Pancreatic and Hepatic Cells from Pluripotent Embryonic Precursor Cells.

23 Molecular Networks in Cardiac Development (Thomas Brand).

23.1 Introduction.

23.2 Implications of Studying Heart Development for Adult Cardiology.

23.3 Model Organisms.

23.4 Anatomical Description of Heart Development.

23.5 Cardiac Induction.

23.6 Transcription Factor Families Involved in Early Heart Induction.

23.7 Tubular Heart Formation.

23.8 Left-Right Axis Development.

23.9 Chamber Formation.

23.10 Outflow Tract Patterning and the Role of the Neural Crest.

23.11 Signals Governing Valve Formation.

23.12 Epigenetic Factors.

23.13 Outlook.

24 Vasculogenesis (Georg Breier).

24.1 Introduction.

24.2 Modes of Blood Vessel Morphogenesis: Vasculogenesis, Angiogenesis and Arteriogenesis.

24.3 Endothelial Cell Differentiation and Hematopoiesis.

24.4 Adult Arteriogenesis and Vasculogenesis.

24.5 Endothelial Cell Growth and Differentiation Factors.

24.6 VEGF and VEGF Receptors.

24.7 Other VEGF Family Members: Involvement in Angiogenesis and Lymphangiogenesis.

24.8 Hypoxia-inducible Factors and Other Endothelial Transcriptional Regulators.

24.9 Outlook.

25 Inductive Signaling in Kidney Morphogenesis (Hannu Sariola and Kirsi Sainio).

25.1 Early Differentiation of the Kidney.

25.2 Regulation of Ureteric Bud Branching.

25.3 Genes Affecting Early Nephrogenesis.

25.4. Signaling Molecules, their Receptors, and the Integrins.

25.5 Transcription Factors.

25.6 Future Perspectives.

26 Molecular and Cellular Pathways for the Morphogenesis of Mouse Sex Organs (Humphrey Hung-Chang Yao).

26.1 Introduction.

26.2 Building the Foundation: Establishment of the Urogenital Ridge.

26.3 Parting the Way: Sexually Dimorphic Development of the Gonad.

26.4 Dimorphic Development of the Reproductive Tracts.

26.5 Morphogenesis of the External Genitalia.

26.6 Summary.

Index.