Atlas of Early Zebrafish Brain Development: A Tool for Molecular Neurogenetics
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Atlas of Early Zebrafish Brain Development: A Tool for Molecular Neurogenetics, Second Edition, remains the only neuroanatomical expression atlas of important genetic and immunohistochemical markers of this vertebrate model system.
It represents a key reference and interpretation matrix for analyzing expression domains of genes involved in Zebrafish brain development and neurogenesis, and serves as a continuing milestone in this research area.
This updated volume provides in-situ hybridized and immunostained preparations of complete series of brain sections, revealing markers of the fundamental stages in the life history of neuronal cells in very high quality preparations and photographic plates. Specific additions to this edition include documentation on the distribution of neurons expressing GABA, dopamine and serotonin, material on the basal ganglia, hypothalamus, and the caudal, segmented part of the diencephalon, new theories on the early organization of the telencephalon and thalamus, and integration of a comparative perspective on the mid- and hindbrain.
- Documentation on the distribution of neurons expressing GABA, dopamine and serotonin
- Material on the basal ganglia, hypothalamus, and the caudal, segmented part of the diencephalon
- New theories about the early organization of the telencephalon and thalamus
- Integration of a comparative perspective on the mid- and hindbrain
Dr. Thomas Mueller
University of Freiburg, Department of Developmental Biology, Freiburg, Germany
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Atlas of Early Zebrafish Brain Development - Dr. Thomas Mueller
Atlas of Early Zebrafish Brain Development
A Tool for Molecular Neurogenetics
Second Edition
Thomas Mueller
Kansas State University, Manhattan, KS, United States of America
Mario F. Wullimann
Ludwig-Maximilians-Universität Munich, Munich, Germany
Table of Contents
Cover image
Title page
Copyright
Preface 2015
Preface 2005
Acknowledgments
Chapter 1: Vertebrate Central Nervous System Development: Introduction
Abstract
1.1 Introductory Remarks: The Order of the Universe
1.2 Major Developmental Stages of the Vertebrate Neural Tube
1.3 Functional Brain Architecture: Mammalian Examples
1.4 Primary and Secondary Neurogenesis in Anamniotes and Amniotes
1.5 The Approach of This Book
Chapter 2: Atlas of Cellular Markers in Zebrafish Neurogenesis: Atlas
Abstract
2.1 Choice and Characterization of Molecular Markers
2.2 Technical Details
2.3 The End of Embryonic Life (2 Days): Outset of Secondary Neurogenesis
2.4 The Early Larva (3 Days): The Emergence of Brain Subdivisions
2.5 The Late Larva (5 Days): Increasing Differentiation
2.6 The Emergence of Transmitter Phenotypes (2 and 3 days): GABA
Chapter 3: Interpretation of Data—How to Use the Atlas: Analysis
Abstract
3.1 General and Local Dynamics of Neurogenesis
3.2 The Generation of Glutamatergic Versus GABAergic Neurons
3.3 The Generation of Modulatory Neurons
3.4 The Exception to the Rule: Peripheral Proliferation and Neurogenesis in the Diencephalon (M1 and M2)
3.5 The Cerebellar and Rhombic Lip Region: Pervasive Tangential Migration
3.6 BrdU Proliferation Assays
Chapter 4: Comparison of Vertebrate Model Systems: Model Systems
Abstract
4.1 Development of Pallial and Subpallial Territories in Vertebrates
4.2 Mammalian Telencephalon: Pallial and Subpallial Gene Expression Patterns
4.3 Teleostean Telencephalon: Evolution and Development of Pallial Territories in the Zebrafish
4.4 Subpallial Territories: Identification and Development of the Zebrafish Basal Ganglia
4.5 Conserved Early Diencephalic Gene Expression Patterns in Vertebrates
4.6 Expression of Basic Helix-Loop-Helix (bHLH) Genes Indicates a Phylotypic Stage of Neurogenesis within a Conserved Vertebrate Forebrain Bauplan
References
Abbreviations
Index
Copyright
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ISBN: 978-0-12-418669-9
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Preface 2015
So, here we are again 10 years down the road. Meanwhile, the zebrafish field has remarkably progressed. The first edition of our atlas promoted new and effective ways of identifying expression patterns in the early zebrafish brain. Clearly, standards for neuroanatomical studies in zebrafish have increased. For example, there is a marked increase in zebrafish-related papers in the Journal of Comparative Neurology if we compare the years prior to the publication of our atlas (1994-2004) to the decade after its publication (2004-2014). A quick PubMed search in these two decades reveals a doubling of hits, that is, 54 versus 118 papers. In similar ways, we find a significant increase in the application of large-scale and 3D confocal imaging technique often using transgenic lines. Still, only precise identification of zebrafish brain structures in a comparative context will allow integration of data from the fields of molecular neuroanatomy, transcriptome, and connectome studies.
To provide maximal consistency with the first edition, we kept the structure of Chapter 1 (historical account) and Chapter 2 (atlas). Notably, we added a number of new plates of immunofluorescence microphotographs to illustrate GABA cell development. In contrast, we greatly modified design and content of Chapters 3 and 4. Chapter 3 now offers a more comprehensive analysis of the development of all major transmitter phenotypes, and in particular glutamatergic and GABAergic neurons. In addition, we describe critical modulatory transmitter systems, such as the dopaminergic, noradrenergic, serotoninergic, histaminergic, and cholinergic neurons. We also comment on glycinergic neurons, and we focus on the two regions with unusual nonperiventricular proliferation in the diencephalon and the cerebellum. Finally, we compare various BrdU approaches and discuss their usefulness for developmental fate studies.
Chapter 4 provides a broad comparative overview. It explains how zebrafish data on neurogenesis are embedded in the vertebrate evo-devo context, in particular in relation to data from the mouse and frog (Xenopus). This chapter also contrasts conserved developmental processes in various vertebrate model systems with ontogenetic peculiarities of zebrafish.
The second edition of the Atlas, thus, offers a more complete and balanced view of neurogenetic events in the zebrafish brain. We also advance a comparative evaluation of these events in the context of key model animals. We hope that this second edition will again be well received in the zebrafish community.
Thomas Mueller; Mario F. Wullimann, Manhattan (Kansas, United States of America) and Martinsried (Germany)—Spring 2015
Preface 2005
No one doubts that methodological revolutions shape the direction of science. For instance, the invention of the microscope led almost directly to the recognition of the cell as the basic module of all organisms. Equally decisive for the scientific progress are ideas and concepts, which sometimes predate their confirmation by adequate methodology. These two closely intertwined processes shape past and present scientific endeavors and are part of human culture created by the efforts of people interconnected by a common interest in similar questions over many decades. The admiration for methodological innovations and the respect for scientific ideas or concepts both represent important foundations of science.
Therefore, the first chapter of this book puts into perspective historically important contributions to the field of early vertebrate central nervous system development. With this, we wish to clarify how the cellular–molecular data delivered in the second, main chapter relate to the larger neurobiological context of neurogenesis in early brain development. The second chapter delivers the actual atlas pages that the readership may use pragmatically to identify certain early zebrafish brain areas. The third chapter takes up the dynamic aspects of how the atlas may be used, be it to elucidate locally differing dynamics of proliferation, determination, and differentiation of neural cells or to implement additional gene expression data. Finally, the fourth chapter delivers a comparative perspective of gene expression patterns between major model animals, especially between mouse and zebrafish.
In addition to delivering a refined early neuroanatomy of the zebrafish brain, the cellular and molecular genetic nature of the data presented in this book allows a starting point for understanding the local differences in the distribution of proliferative, early neuronally determined and differentiating cells and their underlying neurogenetic pathways. The book also is intended to facilitate the use of the zebrafish model animal in many future neurobiologically oriented investigations in basic as well as biomedically relevant research projects.
Acknowledgments
One of the pleasures of finishing a book is to acknowledge the colleagues and friends who gave important feedback, supplied us with probes, and supported the project in various ways. Thanks go to Patrick Blader (Toulouse, France); Uwe Strähle (Karlsruhe, Germany); Michael Lardelli (Adelaide, Australia); Eric Weinberg (Philadelphia, PA, USA); and Rachel McDonald, Ingvild Mikkola, and Steve Wilson (London, UK) for providing probes and antibodies. A big merci goes to Philippe Vernier (Gif-sur-Yvette, France) for enabling us to embark on this project in the first place. Thomas Mueller also thanks Wolfgang Driever (University of Freiburg, Germany) for his support above and beyond what can be expected. In addition, Thomas Mueller is grateful for the generous support of Brian Spooner, Susan Brown, and Gary Conrad from the Division of Biology at Kansas State University. Mario Wullimann thanks Benedikt Grothe (Ludwig-Maximilians-Universität Munich, Germany) for continuing support. Last but not least, this second edition would not have been possible without support and understanding of our families and friends. Thomas Mueller thanks Steffi Dippold; without her presence, work on this book would not have been half as enjoyable.
Chapter 1
Vertebrate Central Nervous System Development
Introduction
Abstract
The first chapter introduces basics of nervous system development. We start with the vertebrate-characteristic morphogenetic event of neurulation. This process leads to the internalized neural tube that forms the entire central nervous system (CNS). In parallel, the formation of neural crest and ectodermal thickenings called placodes develop into the peripheral nervous system and the majority of head sense organs. The neural tube comprises the proliferative neuroepithelium that exclusively produces all neural cell types of brain and spinal cord (including neurons, astro-, and oligodendroglia). Subsequently, neurogenetic processes such as neural proliferation, determination, and differentiation take place within the neural tube wall. In general, these neurogenetic processes include radial migration of neuronal precursors from periventricular to subpial sites. The theoretical framework of the prosomeric model explains emerging neuroanatomical differences along dorsoventral and anteroposterior central nervous axes. Furthermore, the chapter highlights the specific development of the mammalian isocortex, cerebellum, and thalamus with a focus on inside-out versus outside-in patterns of cortex formation/tangential migration events. Finally, it addresses primary (embryonic) and secondary (larval) zebrafish neurogenesis
Keywords
Determination
Differentiation
Neurogenesis
Neurulation
Proliferation
Prosomeric model
1.1 Introductory Remarks: The Order of the Universe
The individual universe each human being mentally carries around is a product of our brain, which most likely represents the most complex object in the world. How does the brain come into existence during development? The ontogeny of the vertebrate central nervous system (CNS: brain and spinal cord) itself is a highly complex yet strongly conserved morphogenetic process. The early vertebrate embryo exhibits three embryonic cellular sheets called germ layers, the most peripheral one being the ectoderm. Its dorsal portion represents the neuroectoderm that develops into the prospective nervous system. The neuroectoderm segregates early from the ventrolaterally lying general ectoderm, which forms the future epidermal skin and its derivatives. Subsequently, the central main portion of the neuroectoderm, the neural plate, is swallowed
by the general ectoderm through the process of neurulation. As a result, the neural plate separates from the general ectoderm and descends into the deep of the embryo, where it develops into a hollow neural tube surrounding a cerebrospinal fluid- (liquor-) filled ventricle. Meanwhile, the general ectoderm closes the temporarily opened dorsal backside of the embryo. The apparent formation along the anteroposterior axis of initially three brain vesicles (forebrain, midbrain, hindbrain) that transform subsequently into five brain vesicles (telencephalon, diencephalon, mesencephalon, metencephalon, myelencephalon) somewhat hides the parallel establishment of finer transverse subdivisions called neuromeres (rhombomeres in the hindbrain, prosomeres in the forebrain, see later). What follows is the differentiation of functional subdivisions of the brain and spinal cord (for example, the optic tectum/superior colliculus, a midbrain sensorimotor integration center, or the hypothalamus, the major control center of visceral processes).
These events of vertebrate CNS formation are accompanied by the emigration of the most lateral portions of the neuroectoderm, the neural folds (Neuralwülste) and some directly adjacent neuroectodermal regions, which are not incorporated into the neural tube during neurulation. These neuroectodermal components comprise the neural crest of the head and trunk and the placodes that are located in the head only. Eventually neural crest and placodes give rise to cells that migrate to their final destination in the adult body, where they form almost all sensory organs and the sensory neurons in dorsal root and cranial nerve ganglia, which innervate them, and the visceral ganglia of the autonomic nervous system. These somatic and visceral ganglia and their associated nerves represent the peripheral nervous system (PNS).
For many decades, scientists have investigated these complex developmental events leading to the formation of a nervous system in various vertebrates, especially in model animals, such as in the African clawed frog Xenopus, the chick, rodents like the mouse and rat, and most recently, the zebrafish, at molecular, cellular, histological, or morphological levels. Thus, a wealth of scientific literature is available, ready to satisfy almost any hunger for information.
Why then the present book? First of all, it integrates knowledge on CNS development coming from classical developmental studies with recent molecular data related to neuro- and gliogenesis. In particular, we will demonstrate the detailed spatiotemporal order of early postembryonic zebrafish brain development using molecular and cellular markers of neuro- and gliogenesis to visualize local differences, embedded in a holistic morphogenetic context. By combining old and new knowledge, we provide a neuroanatomically based molecular atlas of neural development in the zebrafish brain. We hope that such information—beyond delivering a refined molecular neuroanatomy—will prove to be enlightening in the future elucidation of neurogenetic pathways and their mechanisms.
1.2 Major Developmental Stages of the Vertebrate Neural Tube
Historically, scientists have always aimed to identify the fundamental building blocks of the vertebrate brain. In other words, they have tried to determine the basic developmental brain units and to answer the question of how these transform into functional structures of the mature brain. Before going into a more detailed discourse of the development of finer brain subdivisions (see Section 1.3), we will shortly examine the early events of brain morphogenesis relating to the emergence of vesicles and neuromeres, as well as of longitudinal zones, followed by an account on the neuromeric (prosomeric) model and on central nervous neurogenesis. An excellent in-depth historical account on the understanding of vertebrate brain morphogenesis has been given by Nieuwenhuys (1998a,b,c).
1.2.1 Vesicles, Neuromeres, and Longitudinal Zones
The classical description of a sequential appearance of two, three, and then five brain vesicles (i.e., transverse elements) along the anteroposterior vertebrate neural tube axis dates back to von Baer (1828). This view, however, gained popularity in the early twentieth century with the works of von Kupffer (1906) and Johnston (1909). The two-vesicle stage comprises a combined forebrain (prosencephalon) and midbrain (mesencephalon) vesicle, which is set apart by a vertical neural tube constriction from the hindbrain (rhombencephalon) vesicle. This is followed by the three-vesicle stage displaying forebrain, midbrain, and hindbrain vesicles (see Fig. 1) and, finally, by the five-vesicle stage, consisting of telencephalon and diencephalon (together forming the forebrain), mesencephalon, as well as metencephalon and myelencephalon (together forming the rhombencephalon).
Fig. 1 Schematic lateral view of early mouse brain (E 12.5-13.5) shows prosomeric interpretation ( Puelles and Rubenstein, 1993 , 2003 ), including transverse (neuromeres) and longitudinal (columns) elements. Arrows designate anteroposterior axis of neural tube. Abbreviations : AP: alar plate; BP: basal plate; DT: dorsal thalamus (thalamus), FP: floor plate; P1-P3: prosomeres 1-3 (for more details see text); Pr: pretectum; Rh1-Rh8: rhombomeres 1-8; RP: roof plate; sm: somatomotor column; ss: somaotosensory column; T: telencephalon; vm: visceromotor column; vs: viscerosensory column; VT: ventral thalamus (prethalamus).
The subdivision of both forebrain and hindbrain into two separable (transverse) vesicles, each along the anteroposterior axis, arguably is an epiphenomenon, visible only in mammalian embryos that show an enormous early growth of the telencephalic hemispheres. This hypertrophy detracts from the fact that the most rostral vertebrate neural tube in reality includes in addition to the dorsally lying telencephalon also ventrally the smaller hypothalamus. This renders the concept of transverse telencephalic and diencephalic vesicles obsolete because part of the diencephalon (the hypothalamus) is included in a transverse unit with the telencephalon (Puelles and Rubenstein, 1993, 2003). Also, the somewhat later, characteristic mammalian emergence of a large cerebellum and ventral pontine region led to the impression that the medulla oblongata develops from two separable vesicles, the metencephalic one exhibiting cerebellum and pons, and a myelencephalic vesicle posteriorly. Indeed, the dorsal portion of the anteriormost rhombomere specializes into a dorsal cerebellum. In contrast, the ventral pontine region, which relays cortical information to the cerebellum, develops from ventral and fused portions of rhombomeres 1-4 (Aroca and Puelles, 2005; Alonso et al., 2012). This complex development of the anterior hindbrain historically resulted in the misinterpretation that the two enlargements of cerebellum and pons form a true transverse unit, which was called the metencephalon to separate it from the posterior myelencephalon. However, the medulla oblongata does not show a real boundary between these two postulated vesicles; instead, it is rather divided into a higher number of early segmental entities, the rhombomeres (see later discussion and Fig. 1).
In contrast, the three-vesicle stage reflects on fundamental anteroposterior vertebrate brain divisions. Especially the midbrain-hindbrain boundary has been strongly corroborated in modern developmental neurobiology as a singularly definable boundary and signaling center in the vertebrate brain (Marín and Puelles, 1994; Bally-Cuif and Wassef, 1995; Brand et al., 1996; Lumsden and Krumlauf, 1996; Reifers et al., 1998; Wurst and Bally-Cuif, 2001). Similarly, there is clear evidence for cellular lineage restriction (Larsen et al., 2001) and signaling center function (Scholpp and Brand, 2003) at the forebrain-midbrain boundary.
Equally important for the understanding of the vertebrate CNS bauplan are two neural tube flexures, which were also historically noted early (His, 1888, 1893a). The cephalic flexure of the anteroposterior axis is between the mesencephalon and the prosencephalon, and the cervical flexure is between the rhombencephalon and the spinal cord (compare Fig. 1). The result of this bending of the neuraxis is that the forebrain floor is adjacent to the hindbrain floor. The correct recognition of the adequate course of the anteroposterior axis of the neural tube has important consequences for the interpretation of the topology of brain structures.
Whereas the vesicle story just outlined found its way easily into general textbook knowledge, the historical equally early description of neural tube segments or so-called neuromeres did not. Neuromeres represent a finer set of transitory transverse or segmental divisions of the vertebrate neural tube, and they remain, at least partially, controversial to the present day. Vertebrate hindbrain neuromeres (rhombomeres) are set apart from each other by transverse, vertical constrictions and were already described in the nineteenth century (von Baer, 1828; Orr, 1887). Later, similar morphological observations led to the interpretation of neuromeres to extend into midbrain (mesomeres) and forebrain as well (prosomeres; see Fig. 1; Rendahl, 1924; Bergquist, 1932; Vaage, 1969). However, in these early twentieth-century studies, the basis for recognizing transverse neuromeres was descriptive (and, even worse, transitory) morphology. Thus, serious opposition regarding the acceptance of neuromeres as the important building blocks of the CNS arose with its growing functional neuroanatomical understanding, especially by the so-called American school, which was based on the early work of Gaskell (1889) and later widely spread through the activities of Charles Judson Herrick (1868-1960), who is viewed as one of the founding fathers of modern comparative neurology. In this school's well corroborated view, longitudinal functional zones—embryonically represented dorsoventrally in the neural tube as roof, alar, basal, and floor plates (His, 1888, 1893a,b)—were considered the primary subdivisions of the CNS (see Fig. 1). Both the most dorsal (roof plate) and most ventral (floor plate) longitudinal zones exert critical developmental roles, for example, in mediating dorsoventral polarity of the neural tube or in guiding neuronal differentiation processes. In the adult vertebrate CNS, the roof plate gives rise to dorsal midline structures, such as the epiphysis or the choroid plexus, which covers the rhomboid opening of the medulla oblongata, whereas the floor plate develops, for example, into ventral midline glial cells.
The two intermediate longitudinal zones termed the alar and basal plates form pivotal elements of Herrick's concept of functional vertebrate brain and spinal cord organization. Alar and basal plate derivatives form the characteristic dorsoventral arrangement of four functional longitudinal subzones, that is, alar plate derived somato- and viscerosensory columns and basal plate derived viscero- and somatomotor columns as prototypically present in the spinal cord (see Fig. 1). This dorsoventral spinal cord organization of four sensory and motor zones has been used to consistently explain various local specializations (hypertrophies and reductions) in more anterior brain regions—at least into the midbrain. Thus, this concept of longitudinal functional zones understandably gained much acceptance, and it is still discussed in recent textbooks.
A related question is how far anteriorly the vertebrate brain longitudinal zones extend (see Nieuwenhuys, 1998a). Considering alar and basal plates, there were two factions. Kingsbury (1922) believed that the basal plate tapers out at the mesencephalic-diencephalic boundary and that the alar plate alone forms the more anterior brain parts. Similarly, Herrick (1910) had proposed that the basal plate becomes thinner anteriorly and yet would only continue into the hypothalamus. Here, Herrick's original sin comes in: He believed that the more dorsal diencephalic divisions (ventral thalamus, dorsal thalamus, and epithalamus) all represent longitudinal zones (functionally elaborated alar plate subdivisions that he even saw to continue into the telencephalon), which turned out to be a false concept with long-lasting consequences (see later discussion). Kuhlenbeck (publications between 1926 and 1973; see Nieuwenhuys, 1998a) was supportive of Herrick's longitudinal zone concept (including the diencephalon), but highlighted its bauplan nature, disregarding the functional aspect. In contrast, Bergquist and Källén (1954)—similar to His (1888, 1893a,b)—proposed the continuation of both alar and basal plates into the general region of the optic chiasm/preoptic region. Thus, in line with their neuromeric concept, the forebrain prosomeres contained alar and basal plate derivatives. This has the important consequence that dorsal and ventral thalamus (and pretectum, for that matter) represent transverse—not longitudinal—elements along the anteroposterior neural tube axis, which is a now widely accepted concept (see Fig. 1 and following discussion).
Starting in the 1980s, vertebrate brain neuromery has been reconsidered and confirmed. However, a deep schisma exists between today's segmentalists.
Mostly dealing with rhombomeres (Hannemann et al., 1988; Holland and Hogan, 1988; Keynes and Stern, 1988; Lumsden and Keynes, 1989; Murphy et al., 1989; Lumsden, 1990; Trevarrow et al., 1990; Wilkinson and Krumlauf, 1990; Clarke and Lumsden, 1993; Lumsden and Krumlauf, 1996), many recent researchers stress that rigorous criteria for real transverse (neuromeric) neural tube elements (i.e., containing a piece of roof, alar, basal, and floor plates each) are exclusively met by rhombomeres. Among those criteria are glial intersegmental boundaries, repetitive (metameric) segmental generation of comparable neuronal classes and axonal routing in each neuromere, and most important, neuromere-specific cellular lineage restriction (Fraser et al., 1990). These criteria led to the most stringent definition available of a segment or neuromere as constituting a neural compartment (Larsen et al., 2001). Strong complementary supporting evidence from molecular genetic studies showed that various regulatory genes, especially those of the Hox B cluster (Graham et al., 1989; Hunt and Krumlauf, 1992) or other genes, such as Krox20 (Wilkinson et al., 1989a,b; Oxtoby and Jowett, 1993) are hierarchically or specifically expressed respecting rhombomere boundaries, thereby confining positional information to the rhombomeres. Rhombomeric development finally leads