Table of Contents

Contributors ix

Preface xiii

1. Regulation of the Embryonic Cell Cycle During Mammalian
Preimplantation Development 1
N. Palmer and P. Kaldis
1. Introduction 2
2. The Preimplantation Cell Cycle 4
3. Regulation of the Preimplantation Cell Cycle 10
4. Mouse Models of Cell Cycle Regulators as Developmental Tools 13
5. DNA Damage and Checkpoint Signaling in the Preimplantation Embryo 26
6. Concluding Remarks 35
References 36

2. Genome Duplication at the Beginning of Mammalian
Development 55
M.L. DePamphilis
1. Basic Concepts 56
2. Replication Origins Are Established in Two Steps 61
3. The First Mitotic Cell Division Is Universal 68
4. The Second Cell Division Distinguishes Mammals from Nonmammals 70
5. Replication Origins Are Developmentally Regulated 75
6. Genome Duplication Is Restricted to Once Per Cell Division 80
7. Developmentally Programmed Endoreplication 85
8. Cancer and Human Development 90
9. Epilog 93
References 93

3. Zygotic Genome Activation Revisited: Looking Through the
Expression and Function of Zscan4 103
M.S.H. Ko
1. Introduction 104
2. Waves of Gene Activation: Why They Are Transient? 105
3. Why Are ZGA Genes Evolutionarily so Diverse? 107
4. Zscan4: A Gene Identified for Its Specific Expression During ZGA 108
5. Other ZGA-Specific Genes Such as Eif1a-Like Genes and Tcstv1/3 113
6. Heterochromatin Is Opened and Transcribed During ZGA and Z4 Events 115
7. ZGA is Transient: What Has been Opened Must Be Closed 116
8. ZGA Triggers DNA Damages, Which Must Be Repaired 117
9. Correction of Karyotype Abnormality by ZSCAN4 118
10. Commonality Between ZGA-Specific Phenomena and the Z4 Event 119
11. Perspectives 120
Acknowledgments 121
References 121

4. From Meiosis to Mitosis: The Astonishing Flexibility of Cell
Division Mechanisms in Early Mammalian Development 125
L. Bury, P.A. Coelho, and D.M. Glover
1. Introduction 126
2. Coordinating Cell Cycle Regulation with Development 127
3. Fidelity of Chromosome Transmission 135
4. Acentriolar Spindles 141
5. Positioning the Spindle 151
6. Concluding Remarks 155
References 155

5. The Genetic Regulation of Cell Fate During Preimplantation
Mouse Development 173
A.A. Lokken and A. Ralston
1. Introduction 174
2. The Principles of Mouse Genetics 175
3. The Tools of Mouse Genetics 177
4. The Genetic Regulation of the First Cell Fate Decision 179
5. The Genetic Regulation of the Second Cell Fate Decision 188
Acknowledgment 196
References 196

6. Polarity in Cell-Fate Acquisition in the Early Mouse Embryo 203
C.Y. Leung, M. Zhu, and M. Zernicka-Goetz
1. Introduction 204
2. Polarity Axes in Preimplantation Embryos 205
3. Precompaction Polarity 207
4. 8-Cell Embryos: From Compaction Onward 213
5. The Molecular Landscape of Polarization After Compaction 218
6. Summary and Discussion 226
References 227
vi Contents

7. Mouse Embryo Compaction 235
M.D. White, S. Bissiere, Y.D. Alvarez, and N. Plachta
1. The First Change in Cell Shape During Development 236
2. Proposed Mechanisms for Compaction 238
3. Key Cell Decisions During Compaction 244
4. Open Questions About Compaction 249
5. Emerging Techniques and Future Work 250
6. Conclusions 252
References 252

8. Metabolism of Preimplantation Embryo Development:
A Bystander or an Active Participant? 259
K.J. Kaneko
1. Introduction 260
2. Preimplantation Development Overview 262
3. Energy Metabolism 265
4. Energy Metabolism and Yeast Differentiation 278
5. Energy Metabolism and Preimplantation Embryo Development 283
6. Perspective and Future Considerations 295
Acknowledgments 297
References 297

9. Epigenetic Control of Early Mouse Development 311
C.Y. Lim, B.B. Knowles, D. Solter, and D.M. Messerschmidt
1. Introduction 312
2. DNA-Methylation Dynamics During Epigenetic Reprogramming 313
3. Chromatin Remodeling and Dynamics 323
4. Retrotransposons and Noncoding RNAs 334
5. Epigenetics Beyond the Nucleus 339
6. Coda 346
References 347

10. Capturing Identity and Fate Ex Vivo: Stem Cells from the
Mouse Blastocyst 361
V. Garg, S. Morgani, and A.-K. Hadjantonakis
1. Introduction 362
2. TS Cells Represent the TE Lineage 364
3. XEN Cells Represent the PrE Lineage 369
4. Naïve ES Cells Represent the EPI Lineage of the Blastocyst 372
Contents vii
5. EpiSCs Represent the EPI Lineage of the Postimplantation Embryo 378
6. Interconversion of Embryo-Derived Stem Cell Lines 381
7. Concluding Remarks 383
Acknowledgments 384
References 384

11. Species-Specific Variation Among Mammals 401
R.A. Reijo Pera and L. Prezzoto
1. Introduction to Comparative Embryology 402
2. Nonmammalian Development: The Chicken Embryo 403
3. Rabbit Embryo Development 404
4. Bovine Embryo Development 406
5. Overview of Mouse Embryo Development 407
6. Human and Nonhuman Primate Embryo Development 410
7. Species-Specific Genes in Embryo Development 414
8. Summary 416
Acknowledgments 417
References 417

12. Genetic Analysis of Human Preimplantation Embryos 421
S. Garcia-Herrero, A. Cervero, E. Mateu, P. Mir, M.E. Póo, L. Rodrigo,
M. Vera, and C. Rubio
1. Introduction 422
2. Biopsy Strategies 423
3. Application to Monogenic Disorders 426
4. Carriers of Structural Abnormalities 429
5. Aneuploidy Screening 433
References 440

Index 449

viii Contents