Towards a New Neuromorphology Rudolf Nieuwenhuys • Luis Puelles

Towards a New Neuromorphology

123 Rudolf Nieuwenhuys Luis Puelles Netherlands Institute for Department of Human Royal NL Academy of Arts and Sciences and Psychobiology Amsterdam University of Murcia The Netherlands Murcia [email protected] Spain [email protected]

ISBN 978-3-319-25692-4 ISBN 978-3-319-25693-1 (eBook) DOI 10.1007/978-3-319-25693-1

Library of Congress Control Number: 2015955601

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Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.springer.com) Preface

This book owes its origin to a remarkable coincidence. In October 2012 Luis Puelles (LP) and I (RN) decided to organize and realize a highly selective two-person conference. Its aims were twofold: (1) to discuss the ‘state of the art’ in developmental and comparative neuromor- phology, our fields of interest, and (2) to look into the possibility of preparing an elementary overview of recent developments in these fields. At the same time, one of us (RN) was invited to participate in a neuroscience course for a group of talented students in the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, involving a series of intro- ductory lectures as well as dissections of human brains. We (LP and RN) immediately interpreted this invitation as a unique opportunity to realize our aims. An outline of the lectures to be delivered was forwarded to Leipzig and found approval by Prof. Dr. Robert Turner and Dr. Stephan Geyer, the organizers of the course. The lectures, illustrated with Powerpoint slides and delivered during March 19–21, 2013, were well received, and Prof. Turner spontaneously proposed that his Institute would take the initiative to publish them in their entirety. This offer, which perfectly matched our original intentions (see above), was gratefully accepted, but the transformation of the lecture notes and transcripts (see below) into the final text (the present course) turned out to be much more complex and laborious than anticipated, hence the relatively long time interval between the presentation of these lectures and their appearance in print. Afterwards, the mediation of Professor Turner and his Institute in the publication of the book appeared to be unnecessary, because Springer-Verlag was found willing to publish the work. The authors wish to thank Professor Turner and Dr. Geyer for their generous support, Professor L. H. Bannister for critically reading the entire text, and for making many sug- gestions for improvements with respect to content as well as language, Professors L. Medina and J.L. Ferran for reading and offering valuable advice for changes in the parts of section 10 dealing with the concept of homology, Mrs. Sonja Schall, Juliane Dinse, Nancy Muschall, Aline Peter and Christina Schröder for preparing a complete transcript of the videorecorded lectures, Dr. Jenneke Kruisbrink for help with the collection of literature and Mr. Ton Put for help with the illustrations. In concluding this preamble, the invaluable moral and practical support of Mrs. Suzanne Bakker M Sc. in all phases of this project is gratefully acknowledged and finally, we extend our most sincere thanks to our publisher, Springer-Verlag, and their staff—especially Dr. Andrea Pillmann, Dr. Jutta Lindenborn and Mr. Alexander Subbareddy—for their kind help during the production of this book.

Rudolf Nieuwenhuys Luis Puelles

v Contents

Prologue ...... x

Plan of the Course...... xiv

1 From the Classic to Modern Neuromorphology, an Introductory Overview...... 1 1.1 Neural Plate—Neural Groove—Neural Tube ...... 1 1.2 Neural Segments or Neuromeres...... 3 1.3 The So-Called Brain Vesicles...... 5 Excursion 1: Homage to Karl Ernst von Baer (1792–1876) ...... 11 1.4 The Fundamental Morphological Units of the CNS ...... 13 1.5 Topology Versus Topography in (Neuro) Morphology...... 15 1.6 Summary of the Introductory Overview ...... 26

2 The Neural Plate ...... 29 2.1 Structure ...... 29 Insertion: Principles of molecular developmental (neuro)biology) ...... 31 2.2 From Ectoderm to Neurectoderm ...... 37 2.3 Regionalization and Fate Mapping ...... 39

3 From Neural Plate to Neural Tube ...... 45 3.1 Neurulation ...... 45 3.2 Differentiation and Gene Expressions ...... 47 3.3 Summary of Neural Plate and Neurulation ...... 48

4 The Neural Tube ...... 51 4.1 Historical Introduction-1 ...... 51 Excursion 2: The CNS of amphioxus (Branchiostoma lanceolatum ...... 53 Excursion 3: as modified gland cells ...... 59 4.2 Structure of the Neural Tube ...... 61 4.3 Ventrodorsal Regionalization: Longitudinal Zones...... 63 4.4 Anteroposterior Regionalization: Neuromeres ...... 67 4.5 Summary of the Neural Tube ...... 75 Excursion 4: Biodiversity ...... 77 Excursion 5: Helgoland: Evertebrates ...... 83

5 The Axis of the Brain, Its Flexures and Correlates ...... 95 5.1 Flexures of the Axis: Changes During Development ...... 95 5.2 Flexures of the Axis: Differences Among Species ...... 99 5.3 Flexures of the Axis: A Historical Error and Its Correction ...... 101 5.4 Correlates of the Axis: Sulcus Limitans and Alar/Basal Boundary...... 107 5.5 Summary of the Brain Axis ...... 123

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6 The (Complex) Rostral Part of the Brain ...... 125 Summary ...... 130

7 The Natural Coordinate System of the CNS...... 133 Excursion 6: A beautiful brain atlas ...... 137 Summary ...... 140

8 The Fundamental Morphological Units (FMUs) of the CNS ...... 143 8.1 Orientation...... 143 8.2 The Third Dimension ...... 149 8.3 The FMUs Are Radial Entities and Developmental Modules ...... 151 8.4 Developmental Processes Within the FMUs ...... 157 8.4.1 Proliferation of Matrix Cells ...... 157 8.4.2 Formation of Embryonic Layers ...... 163 8.4.3 Radial Migration of Neuroblasts ...... 173 8.4.4 Differentation of Cell Masses and Cortices ...... 177 8.5 Summary of FMUs ...... 198

9 The Structural Pattern, ‘Bauplan’ or ‘Blueprint’ of the CNS ...... 201 9.1 The Overall Structural Pattern ...... 201 9.2 ‘Orthogonalized’ Maps ...... 203 9.3 A More Detailed Structural Pattern: Progenitor Domains in the Embryonic Mammalian CNS...... 205 9.4 Summary of the CNS Structural Pattern...... 208

10 The Development of Grisea ...... 211 10.1 Introduction ...... 211 10.2 Progressive Differentition Within the FMUs...... 213 10.3 The Formation of Plurisegmental Complexes ...... 217 10.4 Tangential Migrations ...... 221 10.4.1 Spinal Cord ...... 221 10.4.2 Branchiomotor and Visceromotor Nuclei in the Rhombencephalon ...... 227 10.4.3 Rhombic Lip ...... 229 10.4.4 Cerebellum...... 235 10.4.5 Locus Coeruleus, Interpeduncular Nucleus and Substantia Nigra ...... 239 10.4.6 Pretectal Region and Hypothalamus...... 241 10.4.7 ...... 243 10.4.8 Subpallium...... 249 10.4.9 Tangential Migrations; Summary and Concluding Remarks . . . . 251 10.5 Overview of the Development of Grisea ...... 253 10.6 The Homologization of Grisea ...... 261 10.6.1 Introductory Note ...... 261 10.6.2 The Swedish School ...... 261 10.6.3 The Principal Homology Criterion...... 263 10.6.4 The First Auxiliary Homology Criterion...... 267 10.6.5 The Second and Third Auxiliary Homology Criteria ...... 269 10.6.6 The Problem of Tangential Migration of Grisea ...... 271 10.6.7 The Problem of Multiple Origins of Grisea...... 271 Contents ix

11 The ‘Wiring’ of the Brain ...... 273 11.1 Fibre Systems...... 273 Excursion 7: Neurotransmission ...... 285 11.2 Development of Fibre Systems ...... 293 11.3 Molecular Studies on the Development of Fibre Systems ...... 299 11.4 The Basic Organization Plan of the ...... 301

12 General Summary, Conclusions and Perspective...... 305 12.1 Antecedents of the New Neuromorphology ...... 305 12.2 The Genoarchitectonic Basis of the New Neuromorphology ...... 306 12.3 Significance of a Common Bauplan ...... 312 12.4 Necessity of a Rigorous Topologic Approach ...... 315 12.5 Molecular Causal Underpinning ...... 316 12.6 New Neuromorphology and Fibre Systems...... 320 12.7 Structure and Function ...... 321 12.8 Final Conclusion...... 323

References...... 325

Index ...... 335 x Towards a New Neuromorphology

Human zygote

The human brain

THE CROWN ON THE CREATION THE MOST HIGHLY ORGANIZED AND THE MOST COMPLEX STRUCTURE IN THE KNOWN UNIVERSE

1 Prologue Prologue

Plate 1 Behold the human brain!! For some, it is the crown of the creation. For many others, the most highly organized and the most complex structure in the known universe. It is quite remarkable that all this has developed from a single fertilized oocyte, just as the entire organism has. The telencephalon or cerebrum is very large. Its surface is strongly folded, and directly, under this surface, there is a highly complex zone of grey matter, known as the cerebral cortex. Due to the folding, only one-third of the cortex is exposed to the free surface of the cerebrum. The surface of the second large structure—the cerebellum—is also folded even more deeply than that of the cerebrum. This brain part also contains a superficial cortical zone, of which only one-tenth borders the free surface. The minute granular neurons of the cerebellum represent up to 75 % of all brain neurons.

xi xii Prologue 2 Prologue

Plate 2 If we compare the adult human brain with that of an embryo of about one month’s gestation, it appears that the cerebrum and the cerebellum, which represent as we have just seen the dominant structures of the adult brain, develop from relatively small primordia or anlagen. And if we compare the adult human brain with that of an adult lamprey, which is the simplest extant vertebrate, we see that in this animal the cerebral hemispheres and the cerebellum are likewise very small brain parts. Note that in the lamprey, the olfactory bulbs, the primary centres for the processing of olfactory stimuli, exceed the cerebral hemispheres in size and that these relations have dramatically changed in the human brain. It probably is a fair estimate that all over the world some hundred thousand people are working on the human brain, not so much on the human brain as a whole, but rather on partial problems—highly complex problems to be sure—and with the aid of very complex techniques. It could be greatly beneficial if all these workers had a common idea about how this brain is fundamentally structured. What is the real essence of this ultra-complex structure? How far does it compare with other vertebrate brains? It is the central aim of this course to highlight the elementary principles of the ontogenetic and evolutionary development of the human brain. xiii xiv lno h Course the of Plan

3 Plan of the Course

Plate 3 As you can see, the course comprises twelve sections. It begins with an introductory overview of the matter to be covered. This is doubtless the most relaxing part of the whole course, because all of what we will be telling you therein will later come back in more detail. The course ends, not surprisingly, with a brief section entitled: General summary, conclusions and perspective. Throughout the course, numerous smaller and larger excursions will be made to domains/aspects/subjects deserving especial attention.

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