P1: FAW/FAW P2: FAW JWDD017-FM JWDD017-ORahilly August 11, 2006 13:18 Char Count= 0 THE EMBRYONIC HUMAN BRAIN i P1: FAW/FAW P2: FAW JWDD017-FM JWDD017-ORahilly August 11, 2006 13:18 Char Count= 0 The brain at the end of the embryonic period (stage 23, 8 postfertilizational weeks). The color scheme used here (telencephalon in yellow, diencephalon in blue, mesencephalon in brown) will be repeated in a number of illustrations throughout the book. ii P1: FAW/FAW P2: FAW JWDD017-FM JWDD017-ORahilly August 11, 2006 13:18 Char Count= 0 THE EMBRYONIC HUMAN BRAIN AN ATLAS OF DEVELOPMENTAL STAGES THIRD EDITION RONAN O’RAHILLY, M.D., D.Sc., Dr.h.c. FABIOLA MULLER,¨ Dr.habil.rer.nat. School of Medicine University of California at Davis Davis, California and Institut d’Embryologie Sp´eciale Universit´e de Fribourg, Fribourg, Switzerland A JOHN WILEY & SONS, INC., PUBLICATION iii P1: FAW/FAW P2: FAW JWDD017-FM JWDD017-ORahilly August 11, 2006 13:18 Char Count= 0 Illustrations on the cover: Ultrasonic in vivo image at 6 weeks showing the fourth ventricle. cf. Fig. 23-35. Courtesy of Dr. Harm-Gerd Blaas. Perspektomat reconstruction at 8 weeks, stage 23. See Fig. 2-1. Oblique section at 7 weeks, stage 20. See Fig. 20-4. Copyright C 2006 by John Wiley & Sons, Inc., Hoboken, NJ. All rights reserved. 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Library of Congress Cataloging-in-Publication Data: ISBN-13: 978-0-471-69462-5 ISBN-10: 0-471-69462-2 Printed in the United States of America 10987654321 iv P1: FAW/FAW P2: FAW JWDD017-FM JWDD017-ORahilly August 11, 2006 13:18 Char Count= 0 In memory of Ernest Gardner, M.D., neuroscientist, colleague, and friend v P1: FAW/FAW P2: FAW JWDD017-FM JWDD017-ORahilly August 11, 2006 13:18 Char Count= 0 ...ceferoitvngrandbon-heur pour le genre humain, fi cette partie, qui eft la plus delicate de toutes, & qui eft fujette ´a des maladies tres-frequentes, & tres-dangereufes, eftoit auffi bien connu¨e, que beaucoup de Philofophes & d’Anatomiftes fe l’imaginent. Niels Stensen, Discovrs svr 1’Anatomie du cerveau, 1669. vi P1: FAW/FAW P2: FAW JWDD017-FM JWDD017-ORahilly August 11, 2006 13:18 Char Count= 0 CONTENTS Preface to the Third Edition ix 1. Historical Aspects 1 2. Techniques 5 3. Prenatal Measurements 9 4. Embryonic Staging 11 5. Prenatal Age 15 6. Terminology 17 7. Early Stages 21 8. Stage 8: The First Appearance of the Nervous System 25 9. Stage 9: The Major Divisions of the Brain 31 10. Stage 10: The Neural Tube and the Optic Primordium 39 11. Stage 11: Closure of the Rostral Neuropore 51 12. Stage 12: Closure of the Caudal Neuropore and the Beginning of Secondary Neurulation 61 13. Stage 13: The Closed Neural Tube and the First Appearance of the Cerebellum 75 14. Stage 14: The Future Cerebral Hemispheres 84 15. Stage 15: Longitudinal Zoning in the Diencephalon 93 16. Stage 16: Evagination of the Neurohypophysis 103 17. Stage 17: The Future Olfactory Bulbs and the First Amygdaloid Nuclei 115 18. Stage 18: The Future Corpus Striatum, the Inferior Cerebellar Peduncles, and the Dentate Nucleus 133 19. Stage 19: The Choroid Plexus of the Fourth Ventricle and the Medial Accessory Olivary Nucleus 149 20. Stage 20: The Choroid Plexus of the Lateral Ventricles, the Optic and Habenular Commissures, and the Interpeduncular and Septal Nuclei 169 21. Stage 21: The First Appearance of the Cortical Plate in the Cerebral Hemispheres 187 22. Stage 22: The Internal Capsule and the Olfactory Bulbs 205 23. Stage 23: The Brain at the End of the Embryonic Period 219 24. Trimester 1, Postembryonic Phase 263 Early Postembryonic Phase 265 Later Postembryonic Phase 285 25. Trimester 2 297 vii P1: FAW/FAW P2: FAW JWDD017-FM JWDD017-ORahilly August 11, 2006 13:18 Char Count= 0 viii CONTENTS 26. Trimester 3 and the Newborn 305 Supplement: Early Postnatal Life 319 Bibliography 323 Glossary 331 1 1 Appendix 1: Changing Lengths of the Brain and its Subdivisions from 3/2 to 5/2 Weeks (Stages 9–16) 341 Appendix 2: Computer Ranking of the Sequence of Appearance of Features of the Brain 343 Appendix 3: Sequence and Stage of Appearance of Median Features of the Brain 349 Appendix 4: Sequence and Stage of Appearance of Tracts of the Brain 351 Appendix 5: Sequence and Stage of Appearance of Features Associated with the Rhombencephalon 353 Index 354 P1: FAW/FAW P2: FAW JWDD017-FM JWDD017-ORahilly August 11, 2006 13:18 Char Count= 0 PREFACE TO THE THIRD EDITION he main objectives of this monograph are to provide The authors’ scheme of the neuromeres, which differs T and to interpret drawings, photographs, and photomi- from others in being based on the human, is detailed here. crographs of the human embryonic brain. The drawings Other topics emphasized include segmentation, not only include at least a lateral view and a median reconstruction of the neural axis both rostrally and caudally, but also that of the brain at each stage, as well as a clear indication of the of occipitocervical differentiation. Stem and crest cells in plane of section of further illustrations, either drawings or the olfactory region are elaborated, and the cerebellum, photomicrographs. Summarizing statements of the mor- the amygdaloid complex, the hippocampal region, and the phological status of the brain at each stage are supplied, corpus striatum are given special attention. and brief statements concerning relevant anomalous con- This edition has been enhanced by the use of color, ditions are included. as well as by the inclusion of more that 100 new illus- The embryonic period proper (the first eight postfer- trations and 26 new tables. Moreover, some representative tilizational weeks) is particularly important because (1) the examples of ultrasonic images have been interspersed. The embryonic brain is extremely difficult to comprehend and definitions formerly given in Chapter 6 have been expanded to visualize, (2) serial sections of first-class quality that considerably and collected as an important Glossary near show the human embryonic brain are rarely accessible, the end of the book. and (3) most major congenital anomalies appear during The Bibliography has been enlarged and brought up that time. A briefer account of the fetal period has been to date. It comprises more than 350 references to the chief included and emphasizes the continuity of development. studies of the prenatal human brain. The profuse literature Despite a general, superficial similarity in the devel- relating to other species, however, is beyond the scope of opment of the brains of various vertebrates, significant, this book. subtle differences exist so that, undoubtedly important as A set of standardized abbreviations, mostly self- are the findings in other species, contributions specifically evident, is used throughout for the illustrations, and a list to the prenatal human brain are as essential as they are of them is placed immediately inside the front cover. fascinating. The number assigned to chapters 8–23 and the first The external and internal structure of the develop- number given to each illustration indicate the develop- ing brain, the primary concern of this book, is an essential mental stage. prolegomenon for subsequent investigations ranging from The authors wish to acknowledge the valuable sup- immunocytochemistry to imaging in vivo. Structural rep- port for their research provided by the U.S. National Insti- resentation, however, needs to be completed by interpre- tutes of Health over many years. Except where otherwise tation. In the present context two necessary components indicated, the photomicrographs as well as many of the of precise interpretation are (1) morphological staging (as photographs are from the Carnegie Collection.