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THE

EMBRYONIC HUMAN BRAIN

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.

THE

EMBRYONIC HUMAN BRAIN

AN ATLAS OF

DEVELOPMENTAL STAGES

THIRD EDITION

RONAN O’RAHILLY,

¨

FABIOLA MULLER,

M.D., D.Sc., Dr.h.c.

Dr.habil.rer.nat.

School of Medicine

University of California at Davis

Davis, California and

Institut d’Embryologie Sp´eciale Universit´ de Fribourg, Fribourg, Switzerland

A JOHN WILEY & SONS, INC., PUBLICATION

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.

Published simultaneously in Canada

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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

10

9

8

7

6

5

4

3

2

1


In memory of

Ernest Gardner, M.D., neuroscientist, colleague, and friend

. . . ce feroit vn grand bon-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.

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


viii CONTENTS

26. Trimester 3 and the Newborn

 

 

305

Supplement: Early Postnatal Life

 

 

319

Bibliography

 

 

323

Glossary

 

 

331

Appendix 1: Changing Lengths of the Brain and its Subdivisions from 3

1

to 5

1

/2

/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

PREFACE TO THE THIRD EDITION

The main objectives of this monograph are to provide and to interpret drawings, photographs, and photomi-

crographs of the human embryonic brain. The drawings include at least a lateral view and a median reconstruction of the brain at each stage, as well as a clear indication of the plane of section of further illustrations, either drawings or photomicrographs. Summarizing statements of the morphological status of the brain at each stage are supplied, and brief statements concerning relevant anomalous conditions are included.

The embryonic period proper (the first eight postfertilizational weeks) is particularly important because (1) the embryonic brain is extremely difficult to comprehend and to visualize, (2) serial sections of first-class quality that show the human embryonic brain are rarely accessible, and (3) most major congenital anomalies appear during that time. A briefer account of the fetal period has been included and emphasizes the continuity of development.

Despite a general, superficial similarity in the development of the brains of various vertebrates, significant, subtle differences exist so that, undoubtedly important as are the findings in other species, contributions specifically to the prenatal human brain are as essential as they are fascinating.

The external and internal structure of the developing brain, the primary concern of this book, is an essential prolegomenon for subsequent investigations ranging from immunocytochemistry to imaging in vivo. Structural representation, however, needs to be completed by interpretation. In the present context two necessary components of precise interpretation are (1) morphological staging (as distinct from mere seriation, such as length or supposed age), without which individual events cannot be arranged in correct sequence, and (2) accurate three-dimensional reconstructions, without which erroneous assumptions of interpretation can be (and frequently are) made. These desiderata, which have been used by the authors in their research over many years, are a unifying feature of this treatise: (1) the Carnegie system of staging originated by Streeter and named and developed by the authors is fundamental to the presentation, and (2) most of the drawings here are based on extremely precise graphic reconstructions prepared by the authors. No similar work is available.

The authors’ scheme of the neuromeres, which differs from others in being based on the human, is detailed here. Other topics emphasized include segmentation, not only of the neural axis both rostrally and caudally, but also that of occipitocervical differentiation. Stem and crest cells in the olfactory region are elaborated, and the cerebellum, the amygdaloid complex, the hippocampal region, and the corpus striatum are given special attention.

This edition has been enhanced by the use of color, as well as by the inclusion of more that 100 new illustrations and 26 new tables. Moreover, some representative examples of ultrasonic images have been interspersed. The definitions formerly given in Chapter 6 have been expanded considerably and collected as an important Glossary near the end of the book.

The Bibliography has been enlarged and brought up to date. It comprises more than 350 references to the chief studies of the prenatal human brain. The profuse literature relating to other species, however, is beyond the scope of this book.

A set of standardized abbreviations, mostly selfevident, is used throughout for the illustrations, and a list of them is placed immediately inside the front cover.

The number assigned to chapters 8–23 and the first number given to each illustration indicate the developmental stage.

The authors wish to acknowledge the valuable support for their research provided by the U.S. National Institutes of Health over many years. Except where otherwise indicated, the photomicrographs as well as many of the photographs are from the Carnegie Collection. The scanning images are included through the kindness of Dr. med. Harm-Gerd Blaas and other colleagues who are credited in the appropriate places. It is a pleasure to thank all at WileyLiss for their encouragement and assistance.

RONAN O’RAHILLY

FABIOLA MULLER¨

Villars-sur Glane,ˆ Switzerland

July 2006

ix



ABBREVIATIONS

a.

Artery

Aff.

Afferent

A.-H.

Adenohypophysis

Amyg.

Amygdaloid region, nuclei, complex

Bas.a.

Basilar artery

BM

Basement membrane

BV

Blood vessel

C

Cervical

Cbl

Cerebellar plate, cerebellum

Ch.

Chiasmatic plate

Ch.tymp.

Chorda tympani

CN

Cranial nerve

CNS

Central nervous system

Comm.

Commissural plate

C-R

Crown-rump length

D1, D2

Diencephalic neuromeres

Di

Diencephalon

Dors.f.

Dorsal longitudinal fasciculus

Eff.

Efferent

End.div.

Endolymphatic diverticulum

Ep.

Epiphysis

Ext.cbl

External cerebellar swelling

Ggl

Ganglion

GL

Greatest length

Hab.-interp.tr.

Habenulo-interpeduncular tract

Hem.

Cerebral hemisphere

Hipp.

Hippocampus

Hyp.-th.sulc.

Hypothalamic sulcus

Hyp.-th.-teg.-tr.

Hypothalamotegmental tract

Infund.

Infundibulum

Int.cbl

Internal cerebellar swelling

Interest.nu.

Interstitial nucleus

Isth.

Isthmus rhombencephali

Isth.rec.

Isthmic recess

I.-v.f.

Interventricular foramen

Lat.f.

Lateral longitudinal fasciculus

Lat.em.

Lateral ventricular eminence

L.l.f.

Lateral longitudinal fasciculus

LMP

Last menstrual period

Long.fiss.

Longitudinal fissure

L.t.

Lamina terminalis

M or Mes.

Mesencephalon

M1, M2

Mesencephalic neuromeres

M.l.f.

Medial longitudinal fasciculus

Mam.

Mamillary region, nuclei, body

Mam. teg.tr.

Mamillotegmental tract

Med. fore.b

Medial forebrain (or prosencephalic)

 

bundle

Med.tectobulb.tr.

Medial tectobulbar tract

Med.em.

Medial ventricular eminence

Mes. tr. 5

Mesencephalic tract of trigeminal

 

nerve

n.

Nerve

Nas.

Nasal plate, pit, sac, septum

N.-H.

Neurohypophysis

Not.

Notochord

NTD

Neural tube defect

Nu.mes.5

Mesencephalic trigeminal nucleus

Nu.post.X

Nucleus of posterior commissure

Olf.bulb

Olfactory bulb

Olf.n.

Olfactory nerve

Olf.tub.

Olfactory tubercle

Opt.

Optic sulcus, vesicle, cup

Opt.stalk

Optic stalk

Ot.

Otic plate, pit, vesicle

Par.

Parencephalon

Post.-lat.fiss.

Posterolateral fissure

Post.X

Posterior commissure