Stem Cells in Developmental Biology, Vol. 60:

This volume of Current Topics in Developmental Biology showcases the research and therapeutic value of stem cells, and is proof of the increasing maturation of the fields of regenerative and molecular medicine. Reviews include: * Therapeutic cloning and tissue engineering to produce functional replacement tissues. * The role of the protein a-synuclein in a host of neurodegenerative diseases, which may be the first to benefit from stem cell therapy. * The curious array of functions in eukaryotic DNA methyltransferase, crucial for normal development and at the core of epigenetics regulation. * Influencing stem cell differentiation with mechanical stress, another example of genes versus the environment. * The process of mammalian hematopoeisis, and inducing it in model organisms with embryonic stem cells. * The regulation of differential parental germline genetic imprinting, central for epigenetics. * The molecular function and regulation of the cystic fibrosis gene, critical for understanding the complete molecular mechanism of this devastating disorder, which might soon be treatable with stem cells. This volume comprehensively describes some of the most current issues in stem cell biology, and is an exciting preview of therapies that may soon be applied in the clinic. It is essential reading for researchers, clinicians, and trainees alike. * Therapeutic Cloning and Tissue Engineering * Structure and function of eukaryotic DNA methyltransferases * Mechanical Signals as Regulators of Stem Cell Fate * Molecular basis for the Chloride Channel Activity of CFTR and the Consequences of Disease Causing Mutations

Contributors

ix

Preface

xi

1 Therapeutic Cloning and Tissue Engineering

Chester J. Koh and Anthony Atala

I. Introduction

1

(1)

II. Principles of Tissue Engineering

2

(3)

III. Stem Cells

5

(1)

IV. Therapeutic Cloning

6

(3)

V. Applications of Tissue Engineering and Therapeutic Cloning

9

(3)

References

12

(6)

2 &alpha-Synuclein: Normal Function and Role in Neurodegenerative Diseases

Erin H. Norris, Benoit I. Giasson, and Virginia M.-Y. Lee

I. Introduction to the Synuclein Protein Family

18

(2)

II. Synuclein in Synaptic Development and Maintenance

20

(2)

III. Synuclein Protein Interactions

22

(1)

IV. Synucleinopathies

23

(7)

V. Structural Properties of oz-Synuclein Protein

30

(3)

VI. Implications of Oxidative and Nitrative Injury in Synucleinopathies

33

(1)

VII. Effects of Oxidation and Nitration on α-Synuclein Fibril Formation

34

(2)

VIII. Possible Role of Pesticides and Other Toxic Chemicals in PD

36

(2)

IX. Transgenic and Nontransgenic Animal Models of Synucleinopathies

38

(1)

X. Concluding Remarks

39

(1)

Acknowledgments

40

(1)

References

40

(16)

3 Structure and Function of Eukaryotic DNA Methyltransferases

Taiping Chen and En Li

I. DNA Methylation: A Heritable Epigenetic Mark

56

(2)

II. Eukaryotic DNA Methyltransferases

58

(14)

III. Function of DNA Methylation

72

(7)

IV. Concluding Remarks

79

(1)

Acknowledgments

80

(1)

References

80

(12)

4 Mechanical Signals as Regulators of Stem Cell Fate

Bradley T. Estes, Jeffrey M. Gimble, and Farshid Guilak

I. Introduction

92

(2)

II. Mechanical Regulation of Limb Development

94

(1)

III. Theoretical Models of Mechanical Stress in Development

95

(2)

IV. In Vivo Experimentation

97

(6)

V. In Vitro Experimentation

103

(18)

VI. Conclusions

121

(1)

Acknowledgment

121

(1)

References

121

(7)

5 Origins of Mammalian Hematopoiesis: In Vivo Paradigms and In Vitro Models

M. William Lensch and George Q. Daley

I. Introduction: The Hematopoietic System

128

(2)

II. Hematopoiesis: De Muribus et Maribus

130

(29)

III. Points of Divergence Between Murine and Human Blood Formation

159

(2)

IV. Hematopoiesis from Embryonic Stem Cells

161

(10)

V. What Remains To Be Learned?

171

(3)

VI. Summary

174

(1)

Acknowledgments

174

(1)

References

175

(22)

6 Regulation of Gene Activity and Repression: A Consideration of Unifying Themes

Anne C. Ferguson-Smith, Shau-Ping Lin, and Neil Youngson

I. Introduction

197

(3)

II. Regulation of Imprinted Gene Activity and Repression

200

(7)

III. A Consideration of Recurrent Themes

207

(3)

References

210

(6)

7 Molecular Basis for the Chloride Channel Activity of Cystic Fibrosis Transmembrane Conductance Regulator and the Consequences of Disease-Causing Mutations

Jackie F. Kidd, Ilana Kogan, and Christine E. Bear

I. Introduction

216

(2)

II. Role of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channel Function in Tissue Physiology and Pathophysiology

218

(2)

III. Cell Biology of CFTR and the Major CF Mutant (&ΔF508)

220

(2)

IV. Quaternary Structure of CFTR

222

(2)

V. The Permeation Pore of CFTR

224

(4)

VI. Molecular Basis for Regulation by Phosphorylation

228

(2)

VII. Molecular Basis for Regulation by Nucleotides

230

(9)

VIII. Future Directions

239

(2)

Acknowledgments

241

(1)

References

241

(10)

Index

251

(10)

Contents of Previous Volumes

261

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Stem Cells in Developmental Biology, Vol. 60: Stem Cells in Development and Disease

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Stem Cells in Developmental Biology, Vol. 60: Stem Cells in Development and Disease

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Table of Contents

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