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Developmental neurobiology, second edition
Neuroscience & Biobehavioral Reviews, Vol. 5, pp. 191-192. Printed in the U.S.A.
Book Review Developmental Neurobiology, Second Edition. Marcus Jacobson. New York: Plenum Press, 1978, 562 pp. WHEN the first edition of this book appeared in 1970, the author claimed he had attempted a selective assembly of facts on the development of the nervous system. In the Preface of this second edition, a note of despair creeps in as the author indicates that the problems with which he must now be concerned are enlarging exponentially while his grasp of them is expanding at a much slower rate. In spite of such perceived misgivings, Jacobson has produced a work of clarity, depth, breadth and impressive scholarship. The reference section includes approximately 3300 citations, yet the author indicates that it is selective and that he has chosen not to provide a literature citation for every documentable statement. The aim of this project is to elaborate main avenues through the research literature leading to an understanding of how the nervous system develops. To accomplish this Jacobson freely acknowledges debt to history and such pioneers as Detwiler, Henderson, Weiss, Saner, and, of course, Ramon y Cajal. The latter utilized the Golgi technique to visualize the full extent of the neuronal processes in a manner unequalled until recent techniques of intracellular dye injection were developed. In this book masses of literature are analyzed in an attempt to find and evaluate general principles of neurological development which hold across species. Although no species favoritism seems intended, the book must reflect the literature and therefore contains abundant references to frogs, salamanders and chicks. Studies on mammals include work on mice, rats and kittens. The task of developmental neurobiology as indicated by the panorama of this book can be stated succinctly. We would like to know the rules of development so that we may understand how various cells of the embryo develop into various types of neurons and glial cells even though they contain the same genome as cells which differentiate into other structures. We would like to know how these cells migrate and differentiate into various types of tissues with distinctive cytoarchitectonics, form circuits over which information can be passed and, most remarkable of all, form circuits which are functional and often topologically precisely organized. Some of the research tools needed to accomplish this prodigious task are described, e.g., the Golgi stain, tissue culture, vital dyes, autoradiography, and the electron microscope. One gets the impression, however, from this treatise that the important discoveries have come not so much from the application of sophisticated, novel technology, but by the patient, careful application of rather simple technology to experiments carefully designed with a clear view of the literature in species where intervention is possible during gestational stages. The organization of the book is logical in that the developmental events are discussed in roughly the same order as these events occur in the developing brain. This book is in no
sense a laboratory manual. Although stages of development of frogs and other organisms are mentioned by conventional number, no diagrams or elaborate definitions are given. There is no glossary although the index is excellent. The book is concerned with issues and g~neral principles, not with providing elaborate, atlas-like pictorial representation of developmental stages. The author apparently assumes the readership is already informed on the fundamentals including essential terminology. The rudiments of how a layer of germinal cells produces glial cells and neurons of considerable variety are covered early in the book. Surprisingly, newly-formed neurons crowd past already differentiated neurons to assume a more peripheral position in the neural tissue only to be bypassed by yet still newer cells migrating to form a brain in this curious "inside-out" fashion. The cerebellar cortex is presented as an excellent model since its cell types are so well differentiated and cytoarchitectonics so precise. The Purkinje cells provide the output from the cerebellar cortex and that output is modulated by the variety of other cells which form excitatory and inhibitory connections with the Purkinje cells. It is interesting that Purkinje identified these large, distinctive cells which bear his name in the cerebellar cortex long before the Golgi technique was available to visualize the complex dendritic aborization of these cells. It was Ramon y Cajal who pushed this technique to its limits. He stopped developmental processes by imbedding tissue at various stages of development in balsam without coverslips (coverslips produced fading of the Goigi stain). He then produced composite drawings from many tissue samples which presented neuronal structures in a clear manner. From this series of still pictures he reconstructed with a great degree of artistic skill and poetic prose the dynamics of development of neuronal tissues. Jacobson makes extensive use of Cajal's drawings in the text. Chapters 4, 5 and 6 deal with the mechanics of the growth and differentiation of neurons and the development of neuronal connections. Without the hyperbole of Cajal, the process of axonal growth is described with a discussion of the growth cone, the discrete branching of the axon only in the vicinity of the target organ, the guidance of growing processes through tissue planes (e.g., along blood vessels), and the possibility that such growth is guided by electrical, mechanical and chemical factors. Once the axons have extablished connections, the dendrites begin to develop. In some neurons, dendrites comprise 90% of the postsynaptic surface. Cajal described the "chaotic period" of neuron development, when dendrites and cell bodies of many neurons sprout spines which will be resorbed in later development failing the establishment of functional connections. The discussion of growth dynamics of axons and dendrites leads inevitably into a discussion of what is probably the most important topic of the book and of this field, i.e.,
Copyright © 1981 A N K H O International Inc.--0149-7634/81/010191-02500.70/0
192 the formation of functional synapses. Fibers growing past dendrites and soma sometimes form synapses and sometimes do not. When they do, the innervation is often topically precise. F o r example, in pyramidal cells of the cerebral cortex excitatory synapses are mainly restricted to dendritic shafts and cell bodies. Jacobson states that the mechanism that controls the formation of synapses is largely unknown despite all the research in synaptogenesis. The book deals very little with behavior; however, for those interested in the behavioral aspects of developmental neural biology, the last two chapters are paramount since it is here that the problem of the establishment of functional synapses with sense receptors and muscles is discussed. Axons grow out of the spinal cord and form synapses with muscle fibers. Initially muscles may be innervated by many axons, but eventually there follows a period of elimination of the polyneuronal innervation such that each muscle fiber comes to be innervated by a single myelinated axon. The establishment of functional spinal reflexes requires that the Ia afferents and the Golgi tendon organ afferents make appropriate connection in the spinal cord. To explain these remarkable sequences, actions of as yet unknown chemicals are assumed. The muscle fibers by chemical means encourage axonal branching. The motoneuron nurtures the muscle, since denervation results in muscular atrophy. Innervation of a muscle fiber with one axon precludes functional innervation with another. Motoneurons which fail to make functional connections are assumed to degenerate perhaps lacking a sustaining chemical produced by a functional neuromuscular synapse. The last chapter deals with important problems in the field--how to explain how neurons form selective connections with other neurons, with epithelial cells and with muscle. Neurons of a particular type synapse on a specific location on another neuron. Neurons in a particular position in one set of neurons, such as the retina, project to one part of another neuronal set, such as the optic tectum. In the 1930's an extreme empiricistic view prevailed to explain these complex events which stated that neural development produces initially equipotential networks of neurons which develop functional specificity with use and experience. Some theories of the neuronal basis of learning assumed that neurons which fire together tend to form a functional organization. Sperry proposed an alternative chemoaffinity theory which took a different point of view, but seemed to require more assumptions. He proposed that specific synapses are
established initially by means of chemical affinities of neurons and muscles in advance of function. This theory is still widely held although now a larger role is attributed to experience. Connections are not made haphazardly, but are formed according to chemical affinities. Neurons recognize each other because of unique chemical qualities. Observations of in vitro cultures do indeed show that cell types may adhere selectively to other cell types. To someone outside this field, it must seem presumptuous to postulate a multitude o f distinct chemical affinites since these chemicals have not yet been identified. Over the last 50 years research on the grafting of supernumerary limbs on amphibians has produced results requiring yet more assumptions. When a limb is grafted next to a normal limb and becomes innervated by the spinal cord, perhaps with nerves other than those which normally innervate this limb, normal coordinated muscle movement is seen which is synchronized with the homologous muscles in a nearby ungrafted limb providing that the surgery is done at the appropriate stage of development. It was inferred that the muscles induced some specification into motoneurons causing them to form appropriate synaptic connections centrally. Jacobson reviews the evidence and questions this assumption. A similar situation was seen regarding the establishment of function for sensory connections. If skin from the dorsal surface o f a tadpole is transplanted to the ventral surface, when the frog reaches the adult form a tactile stimulus applied to the ventral surface will cause the frog to respond as if the stimulus were applied to the dorsal surface. It was hypothesized that the skin graft became innervated by nerves which would not normally innervate it: however, central connections were established which were appropriate for the origin of the skin segment. The type of central connections formed are dictated by the peripheral tissue. Jacobson reviews this evidence in detail and concludes that this interpretation is supported. This book presents developmental neurobiology as a dynamic, exciting field grappling confidently with the problems which were identified many years ago. The writing style is clear and brisk. The scholarship is monumental. This is the definitive book in the field. Charles L. Kutscher Department of Psychology Syracuse University Syracuse, NY 13210
Book Review Developmental Neurobiology, Second Edition. Marcus Jacobson. New York: Plenum Press, 1978, 562 pp. WHEN the first edition of this book appeared in 1970, the author claimed he had attempted a selective assembly of facts on the development of the nervous system. In the Preface of this second edition, a note of despair creeps in as the author indicates that the problems with which he must now be concerned are enlarging exponentially while his grasp of them is expanding at a much slower rate. In spite of such perceived misgivings, Jacobson has produced a work of clarity, depth, breadth and impressive scholarship. The reference section includes approximately 3300 citations, yet the author indicates that it is selective and that he has chosen not to provide a literature citation for every documentable statement. The aim of this project is to elaborate main avenues through the research literature leading to an understanding of how the nervous system develops. To accomplish this Jacobson freely acknowledges debt to history and such pioneers as Detwiler, Henderson, Weiss, Saner, and, of course, Ramon y Cajal. The latter utilized the Golgi technique to visualize the full extent of the neuronal processes in a manner unequalled until recent techniques of intracellular dye injection were developed. In this book masses of literature are analyzed in an attempt to find and evaluate general principles of neurological development which hold across species. Although no species favoritism seems intended, the book must reflect the literature and therefore contains abundant references to frogs, salamanders and chicks. Studies on mammals include work on mice, rats and kittens. The task of developmental neurobiology as indicated by the panorama of this book can be stated succinctly. We would like to know the rules of development so that we may understand how various cells of the embryo develop into various types of neurons and glial cells even though they contain the same genome as cells which differentiate into other structures. We would like to know how these cells migrate and differentiate into various types of tissues with distinctive cytoarchitectonics, form circuits over which information can be passed and, most remarkable of all, form circuits which are functional and often topologically precisely organized. Some of the research tools needed to accomplish this prodigious task are described, e.g., the Golgi stain, tissue culture, vital dyes, autoradiography, and the electron microscope. One gets the impression, however, from this treatise that the important discoveries have come not so much from the application of sophisticated, novel technology, but by the patient, careful application of rather simple technology to experiments carefully designed with a clear view of the literature in species where intervention is possible during gestational stages. The organization of the book is logical in that the developmental events are discussed in roughly the same order as these events occur in the developing brain. This book is in no
sense a laboratory manual. Although stages of development of frogs and other organisms are mentioned by conventional number, no diagrams or elaborate definitions are given. There is no glossary although the index is excellent. The book is concerned with issues and g~neral principles, not with providing elaborate, atlas-like pictorial representation of developmental stages. The author apparently assumes the readership is already informed on the fundamentals including essential terminology. The rudiments of how a layer of germinal cells produces glial cells and neurons of considerable variety are covered early in the book. Surprisingly, newly-formed neurons crowd past already differentiated neurons to assume a more peripheral position in the neural tissue only to be bypassed by yet still newer cells migrating to form a brain in this curious "inside-out" fashion. The cerebellar cortex is presented as an excellent model since its cell types are so well differentiated and cytoarchitectonics so precise. The Purkinje cells provide the output from the cerebellar cortex and that output is modulated by the variety of other cells which form excitatory and inhibitory connections with the Purkinje cells. It is interesting that Purkinje identified these large, distinctive cells which bear his name in the cerebellar cortex long before the Golgi technique was available to visualize the complex dendritic aborization of these cells. It was Ramon y Cajal who pushed this technique to its limits. He stopped developmental processes by imbedding tissue at various stages of development in balsam without coverslips (coverslips produced fading of the Goigi stain). He then produced composite drawings from many tissue samples which presented neuronal structures in a clear manner. From this series of still pictures he reconstructed with a great degree of artistic skill and poetic prose the dynamics of development of neuronal tissues. Jacobson makes extensive use of Cajal's drawings in the text. Chapters 4, 5 and 6 deal with the mechanics of the growth and differentiation of neurons and the development of neuronal connections. Without the hyperbole of Cajal, the process of axonal growth is described with a discussion of the growth cone, the discrete branching of the axon only in the vicinity of the target organ, the guidance of growing processes through tissue planes (e.g., along blood vessels), and the possibility that such growth is guided by electrical, mechanical and chemical factors. Once the axons have extablished connections, the dendrites begin to develop. In some neurons, dendrites comprise 90% of the postsynaptic surface. Cajal described the "chaotic period" of neuron development, when dendrites and cell bodies of many neurons sprout spines which will be resorbed in later development failing the establishment of functional connections. The discussion of growth dynamics of axons and dendrites leads inevitably into a discussion of what is probably the most important topic of the book and of this field, i.e.,
Copyright © 1981 A N K H O International Inc.--0149-7634/81/010191-02500.70/0
192 the formation of functional synapses. Fibers growing past dendrites and soma sometimes form synapses and sometimes do not. When they do, the innervation is often topically precise. F o r example, in pyramidal cells of the cerebral cortex excitatory synapses are mainly restricted to dendritic shafts and cell bodies. Jacobson states that the mechanism that controls the formation of synapses is largely unknown despite all the research in synaptogenesis. The book deals very little with behavior; however, for those interested in the behavioral aspects of developmental neural biology, the last two chapters are paramount since it is here that the problem of the establishment of functional synapses with sense receptors and muscles is discussed. Axons grow out of the spinal cord and form synapses with muscle fibers. Initially muscles may be innervated by many axons, but eventually there follows a period of elimination of the polyneuronal innervation such that each muscle fiber comes to be innervated by a single myelinated axon. The establishment of functional spinal reflexes requires that the Ia afferents and the Golgi tendon organ afferents make appropriate connection in the spinal cord. To explain these remarkable sequences, actions of as yet unknown chemicals are assumed. The muscle fibers by chemical means encourage axonal branching. The motoneuron nurtures the muscle, since denervation results in muscular atrophy. Innervation of a muscle fiber with one axon precludes functional innervation with another. Motoneurons which fail to make functional connections are assumed to degenerate perhaps lacking a sustaining chemical produced by a functional neuromuscular synapse. The last chapter deals with important problems in the field--how to explain how neurons form selective connections with other neurons, with epithelial cells and with muscle. Neurons of a particular type synapse on a specific location on another neuron. Neurons in a particular position in one set of neurons, such as the retina, project to one part of another neuronal set, such as the optic tectum. In the 1930's an extreme empiricistic view prevailed to explain these complex events which stated that neural development produces initially equipotential networks of neurons which develop functional specificity with use and experience. Some theories of the neuronal basis of learning assumed that neurons which fire together tend to form a functional organization. Sperry proposed an alternative chemoaffinity theory which took a different point of view, but seemed to require more assumptions. He proposed that specific synapses are
established initially by means of chemical affinities of neurons and muscles in advance of function. This theory is still widely held although now a larger role is attributed to experience. Connections are not made haphazardly, but are formed according to chemical affinities. Neurons recognize each other because of unique chemical qualities. Observations of in vitro cultures do indeed show that cell types may adhere selectively to other cell types. To someone outside this field, it must seem presumptuous to postulate a multitude o f distinct chemical affinites since these chemicals have not yet been identified. Over the last 50 years research on the grafting of supernumerary limbs on amphibians has produced results requiring yet more assumptions. When a limb is grafted next to a normal limb and becomes innervated by the spinal cord, perhaps with nerves other than those which normally innervate this limb, normal coordinated muscle movement is seen which is synchronized with the homologous muscles in a nearby ungrafted limb providing that the surgery is done at the appropriate stage of development. It was inferred that the muscles induced some specification into motoneurons causing them to form appropriate synaptic connections centrally. Jacobson reviews the evidence and questions this assumption. A similar situation was seen regarding the establishment of function for sensory connections. If skin from the dorsal surface o f a tadpole is transplanted to the ventral surface, when the frog reaches the adult form a tactile stimulus applied to the ventral surface will cause the frog to respond as if the stimulus were applied to the dorsal surface. It was hypothesized that the skin graft became innervated by nerves which would not normally innervate it: however, central connections were established which were appropriate for the origin of the skin segment. The type of central connections formed are dictated by the peripheral tissue. Jacobson reviews this evidence in detail and concludes that this interpretation is supported. This book presents developmental neurobiology as a dynamic, exciting field grappling confidently with the problems which were identified many years ago. The writing style is clear and brisk. The scholarship is monumental. This is the definitive book in the field. Charles L. Kutscher Department of Psychology Syracuse University Syracuse, NY 13210