Studies of oogenesis occupy an important place in current in vestigations in developmental biology. Today no one has any doubt whatsoever that oogenesis is not just the prelude to development, but is development itself, and a very essential part of it. These words of an eminent Soviet scientist, B. L. As taurov, taken by T. B. Aizenshtadt as an epigraph to her chapter in this book, make a good epigraph for the entire book. It is now clear that during oogenesis not only vast reserves of ribosomes and mitochondria, of yolk, carbohydrates, and lipids, and of enzymes for protein and nucleic acid synthesis and for carbohydrate and fat metabolism (which ensures the energy supply and metabolism of the oocyte and the developing embryo) are formed, but also long-lived mRNA and proteins are synthesized, which determine both the completion of oocyte maturation and the initial stages of embryonic development. In the last 15-20 years, the use of molecular biology methods, electron microscopy, autoradiography, and microsurgical methods of experimental embryology in studying the pre-embryonic development of animals has greatly increased our knowledge of oogenesis. This has led to the need to systematize the data obtained, to reinter pret old ideas, and to review the results obtained by new research trends which have emerged in the last few years and which are of general biological interest. Such a task was undertaken in the book Sovremennye Problemy Oogeneza (Current Problems of Oogenesis), published in 1977 (in Russian)."

The subject of this book is reproduction-specifically, the interplay between reproductive physiology (especially neural and endocrine events) and behavior. In presenting this topic, there are two expository goals. The first is to study repro- duction at all of the major levels of biological organization-from the molecular (e. g. , hormone receptors in the brain), through the cellular (e. g. , ovarian morphogene- sis), systemic (e. g. , operation of the hypothalamo-pituitary-ovarian axis), and the organismic levels of organization. Analogously, behavior is treated from the most molecular, elementary, and fundamental components (e. g. , copulatory reflexes), through behavior in the reproductive dyad (e. g. , analysis of female sexual behav- ior), to complex social behavior (e. g. , the interaction of social context and behav- ioral sex differences). To the extent that these levels of biological and behavioral organization rep- resent a "vertical axis" in behavioral neurobiology, a second goal is to treat the "horizontal axis" of biological organization, viz. , time. There are, therefore, treat- ments of evolutionary origins (e. g. , a phylogenetic survey of psychosexual differ- entiation), genetic origins in the individual (e. g. , sexual organogenesis), ontoge- netic development (e. g. , behavioral sexual differentiation), and the immediate physiological precursors of behavior (e. g. , hormonal and nonhormonal initiation of maternal behavior). In addition to tracing the origins of reproduction and reproductive behavior, one extends the time-line from the behavior to its physio- logical consequences (e. g. , neuroendocrine consequences of sexual behavior).

With a few notable exceptions, mammalian preimplantation embryos grown in vitro are likely to exhibit sub-optimal or retarded development. This may be manifested in different ways, depending on the species and on the stage(s) of embryonic development that are being examined. For example, bovine embryos often experience difficulty in cleaving under in vitro conditions, and usually cease development at about the 8-cell stage (Wright and Bondioli, 1981). The block to development is stage-dependent; embryos cultured for 24 hr from the I-cell stage are much more capable of developing into viable blastocysts after transfer to oviducts than embryos cultured for 24 hr from the 4-cell stage prior to transfer (Eyestone et oZ. , 1985). Similar problems with in vitro embryo development are encountered in other species. Pig embryos can be grown up to the 4-cell stage in vitro but usually no further (Davis and Day, 1978). In the golden hamster, in the rat and in many outbred strains of mice, development of zygotes in vitro is blocked at the 2-cell stage (Yanagimachi and Chang, 1964; Whittingham, 1975). Even with some inbred mouse strains, embryo development is reduced if very early cleavage stages are used as the starting point for in vitro culture (Spielmann et oZ. , 1980). A common finding is that embryos grown in vitro have reduced cell counts (Harlow and Quinn, 1982; Kane, 1985) and their viability is reduced (Bowman and McLaren, 1970; Papaioannou and Ebert, 1986) compared to equivalent developmental stages recovered from mated animals.

HOWARD C. TAYLOR, JR. Medicine, through its long history, has continually striven to enlarge its scope. Success in these endeavors has come in sudden bursts with long intervals of relative quiescence between. As a result of the spectacular discoveries in the basic sciences during the last decades, medicine is again in a period of revolutionary advance in many fields. One of these is the subject of this report, "The Intrauterine Patient." Until recently the fetus signalized his presence only by the mother's enlarging abdomen and by his own movements, perceived by the preg nant woman herself and evident to the examining midwife and physician. Later, the sounds of the fetal heart heard by auscultation and the varia tions in its rate became the single important means by which the welfare of the fetus might be roughly determined and threats to his survival per haps detected. Otherwise, the fetus remained isolated, his condition unknown and any therapy consequent on diagnosis, except for the induc tion or termination of labor, nonexistent."

The cause of many of the adverse reproductive outcomes and developmental diseases among offspring is not well understood. Most of the epidemiologic and experimental animal research has focused on the relationship between maternal exposures including medications, tobacco smoke, alcohol, infections, and occupation and the occurrence of spontaneous abortion, low birth weight, and birth defects. The potential role of paternal exposures has not been investigated as extensively despite long-standing animal research that demonstrates the induction of mutations in the male germ cell after exposure to certain agents and subsequent reproductive failure or early pregnancy loss. Given this relative lack of interest, acquisition of epidemiologic data and the development of a definitive model or mechanism for potential male-mediated effects has been hindered. However, recent laboratory and epidemiologic investigations have suggested that paternal exposures may be more important than previously suspected. This topic has been termed by some as "male-mediated developmental toxicity. " This is meant to refer to the effects of exposures and other factors relating to the male parent that result in toxicity to the conceptus and abnormal development. The developmental endpoints of interest can include fetal loss, congenital abnormalities, growth retardation, cancer, and neurobehavioral effects. These effects may operate through a variety of mechanisms including gene mutation, chromosomal aberrations, seminal fluid transfer of toxicants and epigenetic events.

The aimoftheHypospadiasand Genital Symposium, held at theUniversityof California,SanFrancisco,wastoprovideaforumforauthoritativeinvestigatorswhoare activelyinvolvedinthevariousdisciplineswhichdefinetheleadingedgesofhypospadias and genital research. It is important for such investigators to continue to meet for the purpose of discussing the latest developments in their individual fields, to analyze the significanceofcurrent research, to discuss new tactics for unresolved problems and to develop new theories andapproaches asneeded. The two day conference on hypospadiasandgenitaldevelopment research was organizedintothreesections: 1)HumanStudies;2)MechanismofGenitalDevelopment; and 3) Endocrine Disruptors and Sexual Dimorphism in the Animal Kingdom. Each sessionwasintroducedbyanexpertmoderatorfollowedtheinvitedspeakerswithtimefor extensiveinteractionbetweeninvestigators. Thisbookdocumentstheproceedingsofthe HypospadiasandGenitalDevelopmentSymposium. Iwould especially like to thank Kari Gaudette for editorial assistants, Cynthia Ashe, Selcuk Yucel, Antonio Souza and the administrative staffinthe Departmentof Urology. Ihopeyoufindthisresourceuseful. Laurence S. Baskin,M. D. ProgramChair ChiefPediatricUrology UCSF vii ACKNOWLEDGEMENTS Supportforthissymposiumisgratefullyacknowledged TheNationalInstituteofHealthGrant#R13DK*HDS997 UCSFDepartmentofUrology AmericanUrologicAssociation CONTENTS Introduction...1 SECTIONI. HUMANSTUDIES EpidemiologyofHypospadias...*...*...25 J. DavidErickson EndocrineEvaluationofHypospadias...31 G. HyunandT. Kolon EndocrineAbnormalitiesinBoyswithHypospadias...45 R. I. Silver GeneticandClinicalStudiesonHypospadias...***...**...*...73 A. Nordenskjold SECTIONII. MECHANISMOFGENITALDEVELOPMENT DevelopmentofthePenileUrethra. . 87 G. CunhaandL. Baskin AnatomicalStudiesoftheMouseGenitalTubercle...103 L. Baskin,W. Liu,J. Bastacky,andS. Yucel AnatomicalStudiesoftheFibroblastGrowthFactor-l0Mutant,Sonic HedgeHogMutant,andAndrogenReceptorMutantMouseGenital Tubercle...*. **. . 123 S. Yllcel,W. Liu,DCordero,A. Donjacour,G. Cunha,andL. Baskin DevelopmentalGeneticsofHypospadias...149 M. Cohn xiii xiv Contents DevelopmentoftheMouseExternalGenitalia: UniqueModelof Organogenesis...159 K. Suzuki, K. Shiota,Y. Zhang,L. Lei,andG. Yamada NewConceptsontheDevelopmentoCtheVagina...173 E. Shapiro. H. Huang,andX. R. Wu SECTIONIII. ENDOCRINEDISRUPTORSANDSEXUAL DIMORPHISMINTHEANIMALKINGDOM EndocrineDisruptionOverview: AreMalesatRisk? 189 T. Colburn EndocrineDisruptionandHypospadias...203 G. Steinhardt Toxicant-InducedHypospadiasintheMaleRat * 217 L. E. Gray. . I. Ostby,J. Fun,C. Wolf,C. Lambright,V. Wilson, and N. Noreiga MasculinizationofFemaleMammals: LessonsfromNature...243 N. J. PI:H'candS. Glickman Index...255 SectionI Introduction HYPOSPADIAS LaurenceS. Baskin* M. D. ,FAAP 1.

The overall scope of this new series will be to evolve an understanding of the genetic basis of (1) how early mesoderm commits to cells of a heart lineage that progressively and irreversibly assemble into a segmented, primary heart tube that can be remodeled into a four-chambered organ, and (2) how blood vessels are derived and assembled both in the heart and in the body. Our central aim is to establish a four-dimensional, spatiotemporal foundation for the heart and blood vessels that can be genetically dissected for function and mechanism. Since Robert DeHaan's seminal chapter "Morphogenesis of the Vertebrate Heart" published in Organogenesis (Holt Rinehart & Winston, NY) in 1965, there have been surprisingly few books devoted to the subject of cardiovascular mor phogenesis, despite the enormous growth of interest that occurred nationally and internationally. Most writings on the subject have been scholarly compilations of the proceedings of major national or international symposia or multiauthored volumes, often without a specific theme. What is missing are the unifying concepts that can make sense out of a burgeoning database of facts. The Editorial Board of this new series believes the time has come for a book series dedicated to cardio vascular morphogenesis that will serve not only as an important archival and didac tic reference source for those who have recently come into the field but also as a guide to the evolution of afield that is clearly coming of age.

This volume comprises normal tables (description of normal development) for protozoa and invertebrates widely used in developmental biology studies. The species chosen reflect their advantages for laboratory studies, the information avail able, and their availability for experimentation. Chapter 11, which contains the normal tables for the starfish Asterina pectinifera, was written specially for this edi tion, which is the invertebrate section of the revised and augmented translation of Ob"ekty Biologii Razvitiya published in Russian in 1975 as a volume in the series of monographs Problemy Biologii Razyitiya (Problems of Developmental Biology) by Nauka Publishers, Moscow. The description of every species is preceded by an introduction in which the advantages of working with the particular animal are stated and the problems stud ied (with the main references) are outlined. Data are also provided on its taxonomic status and distribution of the animal, and conditions of keeping the adult animals in laboratory. Methods of obtaining gametes, methods of artificial fertilization, meth ods of rearing embryos and larvae, and tables of normal development are also given."

This book has evolved by processes of selection and expansion from its predecessor, Practical Scanning Electron Microscopy (PSEM), published by Plenum Press in 1975. The interaction of the authors with students at the Short Course on Scanning Electron Microscopy and X-Ray Microanalysis held annually at Lehigh University has helped greatly in developing this textbook. The material has been chosen to provide a student with a general introduction to the techniques of scanning electron microscopy and x-ray microanalysis suitable for application in such fields as biology, geology, solid state physics, and materials science. Following the format of PSEM, this book gives the student a basic knowledge of (1) the user-controlled functions of the electron optics of the scanning electron microscope and electron microprobe, (2) the characteristics of electron-beam-sample inter actions, (3) image formation and interpretation, (4) x-ray spectrometry, and (5) quantitative x-ray microanalysis. Each of these topics has been updated and in most cases expanded over the material presented in PSEM in order to give the reader sufficient coverage to understand these topics and apply the information in the laboratory. Throughout the text, we have attempted to emphasize practical aspects of the techniques, describing those instru ment parameters which the microscopist can and must manipulate to obtain optimum information from the specimen. Certain areas in particular have been expanded in response to their increasing importance in the SEM field. Thus energy-dispersive x-ray spectrometry, which has undergone a tremendous surge in growth, is treated in substantial detail.

Many complex molecular interactions are involved in the development of the mammalian brain. Molecules serving as guidance cues for migratory cells, growing axons and for recognition of postsynaptic targets are a major topic for research because they are directly involved in the formation of neuronal circuits, thus creating the foundation for subsequent functional refinement through interactions with the environment. In addition, most guidance cue molecules are also involved in plasticity, damage repair and regeneration in the adult brain.

This volume reviews current knowledge on major classes of molecules involved in: guidance of growing axons; tau proteins involved in the establishment of axonal polarity, outgrowth and contact recognition; gangliosides and lectins involved in neuronal migration, neurite outgrowth and contact recognition; and myelin molecules that inhibit nerve regeneration.

The World Congress of In Vitro Fertilization and Alternate Assisted Reproduction, held in Jerusalem, Israel, 2-7 April, 1989, was the sixth in the sequence of these Congresses, but was the first to emphasize the major importance and the place of assisted reproductive technologies in the treatment of infertility. The eternal City of Jerusalem witnessed the gathering of more than 1500 participants from allover the world who shared and exchanged knowledge and up-to-date experience in this ever-evolving field. The high quality scientific contributions to the Congress culminated in the publication of this Proceedings. It embraces all-important aspects in the field of in vitro fertilization and alternate assisted reproduction. Papers on controversies and diversities of methods to stimulate the ovaries, imaging techniques, basic research and state-of-the-art papers on ovarian physiology, the role of GnRH and its analog, clinical aspects of IVF treatment and cryopreservation, up-to-date techniques in assisted reproductive technologies that are quickly developing in conjunction with IVF, were included. When should IVF be preferable to surgery? What are the ex pected up-to-date world results and what are the psychological, moral, ethical and religious implications? These are all the concerns of the treating team and are addressed here. Male factor infertility remains a frustrating problem, but advances in the understanding of sperm-egg interaction, sperm evaluation and preparation are reported. Micromanipulation emerges as a possible alternative to bring some relief to this problem, but it also promises to be central in promoting the field of prenatal genetic analysis."

Early embryonic loss is a continuing social and economic global problem. In human populations the estimates of interruptions early in pregnancy range from 35-60%. In animal husbandry (swine, ruminants) fully 30% of pregnancies fail to survive early events of gestation. The futility associated with this persistant high risk is even more unsettling because of advances made in assisted reproductive technology which, although this very selective methodology has added to our knowledge of embryo-endometrial interactions, has resulted in a birth rate of only 14%. These studies have instigated comparisons of the live relative contributions of the embryo and the uterus to the outcome of pregnancy. These analyses have shown that we have learned significantly less about the role of the uterus in deciding the outcome of either natural or assisted pregnancies. In 1979 a quotation by George Corner was used to set the tone of a meeting that was devoted to discussion of the cellular and molecular aspects of implantation. In spite of the proliferation in research activity which occurred in the following 15 years our real understanding of the embryo transfer process has fallen short of our expectations. We use the Corner quotation, once again, to preface this symposium so that we may recall that the fundamental nature of the process which regulates embryo-endometrial interactions still escapes us.

The auditory system has a remarkable ability to adjust to an ever-changing environment. The six review chapters that comprise Plasticity of the Central Auditory System cover a spectrum of issues concerning this ability to adapt, defined by the widely applicable term "plasticity." With chapters focusing on the development of the cochlear nucleus, the mammalian superior olivary complex, plasticity in binaural hearing, plasticity in the auditory cortex, neural plasticity in bird songs, and plasticity in the insect auditory system, this volume represents much of the most current research in this field. The volume is thorough enough to stand alone, but is closely related a previous SHAR volume, Development of the Auditory System (Volume 9) by Rubel, Popper, and Fay. The book fully addresses the difficulties, challenges, and complexities of this topic as it applies to the auditory development of a wide variety of species.

Each new volume of this publication brings the privilege of expressing some of my thoughts on subjects of interest to its readers. In the past year or so public concern about environmental and societal dangers has largely turned to those of cosmic proportion-Chernobyl, the thinning ozone layer, AIDS, and the like-and thankfully our subject matter has been allowed a respite. Even the miniepidemic of craniofacial and other malformations caused by the retinoid antiacne drug Accutane made no headlines. Incidentally, this might have been a tragedy of far greater proportions had it not been nipped in the bud by the historical ground work that quickly permitted it to be recognized as due to an environ mental teratogen-the sort of fact the public and authorities inadequately appreciate. But there is a warning connected with this abeyance of media focus on teratological matters. Disquiet over cosmic imbalances will sub side as they are corrected or horrendous projections fail to materialize, and even cures for dread infectious diseases, or Puritan revolution in terdicting such plagues, will be forthcoming, and these things will occur long before congenital malformations are no more. And as the year-in and year-out recurrence of over 100,000 an nual births of seriously malformed infants in the United States alone continues to force itself on the public consciousness, we can expect a heightened demand that "a cure" be found, because "if we can land a man on the moon, if we can prevent polio, why can't we . . ."

Why Efforts to Expand the Meaning of "Teratogen" Are Unacceptable Disagreement about nomenclature in teratology is not new. Dissent even about the very fabric of the discipline-what congenital malformations consist of-has often been voiced. Time, instead of resolving such diffi culties, has sometimes worsened them. For example, in the past it was agreed that congenital malforma tions are abnormalities of structure present at birth, but differences of opinion concerning where the line between normal and abnormal was to be drawn prevailed. It was obvious that, in order to discover the causes of congenital malformations and cast strategies for their prevention, it would be necessary to have knowledge of the baseline of their frequency, and that this required uniformity of definition of terms. Since malfor mations of primary social concern are those having grave outcomes (and are, paradoxically, also the commonest ones), it is logical that such condi tions were the first consideration of investigators and were the defects whose frequency was considered to comprise the required baseline.

In the last decade, since the publication of the first edition of Scanning Electron Microscopy and X-ray Microanalysis, there has been a great expansion in the capabilities of the basic SEM and EPMA. High resolution imaging has been developed with the aid of an extensive range of field emission gun (FEG) microscopes. The magnification ranges of these instruments now overlap those of the transmission electron microscope. Low-voltage microscopy using the FEG now allows for the observation of noncoated samples. In addition, advances in the develop ment of x-ray wavelength and energy dispersive spectrometers allow for the measurement of low-energy x-rays, particularly from the light elements (B, C, N, 0). In the area of x-ray microanalysis, great advances have been made, particularly with the "phi rho z" Ij)(pz)] technique for solid samples, and with other quantitation methods for thin films, particles, rough surfaces, and the light elements. In addition, x-ray imaging has advanced from the conventional technique of "dot mapping" to the method of quantitative compositional imaging. Beyond this, new software has allowed the development of much more meaningful displays for both imaging and quantitative analysis results and the capability for integrating the data to obtain specific information such as precipitate size, chemical analysis in designated areas or along specific directions, and local chemical inhomogeneities."

"The old order changeth, yielding place to new. " When Tennyson wrote this, he was unfamiliar with the pace of modem science else he would have said the new is displaced by the newer. When Gilbert and I gathered the papers for the first edition of this overview of metamorphosis, we aimed to provide a broad basis upon which the experimental analysis of the developmental changes called metamorphosis could proceed. We were both aware then that with the new techniques of biochemistry and with the revolutionary breakthrough to the nature of the gene, countless new possibilities were being opened for the exploration of the molecular basis of development. The resources offered by metamorphic changes offered unique opportunities to trace the path from gene to phenotype. Our expectations were high. I visited Larry Gilbert and Earl Frieden in their laboratories and saw with envy how far advanced they were then in the use of molecular methods of analysis. I had started on a different approach to develop an in vitro test for thyroid action on amphibian tissue. But circumstances limited my own progress to the initial delim itation of the technical possibilities of the in vitro system. Only from the sidelines could I watch the steady if slow progress of biology in penetrating the maze of molecular events by which animal tissues re spond to hormonal and other developmental factors."

Our understanding of the molecular mechanisms involved in mammalian brain development remains limited. However, the last few years have wit nessed a quantum leap in our knowledge, due to technological improve ments, particularly in molecular genetics. Despite this progress, the available body of data remains mostly phenomenological and reveals very little about the grammar that organizes the molecular dictionary to articulate a pheno type. Nevertheless, the recent progress in genetics will allow us to contem plate, for the first time, the integration of observation into a coherent view of brain development. Clearly, this may be a major challenge for the next century, and arguably is the most important task of contemporary develop mental biology. The purpose of the present book is to provide an overview that syn thesizes up-to-date information on selected aspects of mouse brain devel opment. Given the format, it was not possible to cover all aspects of brain development, and many important subjects are missing. The selected themes are, to a certain extent, subjective and reflect the interests of the contributing authors. Examples of major themes that are not covered are peripheral nervous system development, including myelination, the development of the hippocampus and several other CNS structures, as well as the developmental function of some important morphoregulatory molecules."

Developmental biology took shape between 1880 and the 1920s Basic concepts like the developmental role of chromosomes and the germ plasm (today's genome), self differentiation, embryonic regulation and induction, gradients and organizers hail from that period; indeed, the discipline was defined as a whole by the programmatic writings of Wilhelm Roux as early as 1889. The present essays cover the period up to the Nobel prize-winning work of Hans Spemann and Hilde Mangold. They were originally published in Roux's Archives of Developmental Biology, from Vol. 200 onward to the journal's centennial issues in 1995/96. The essays aim at introducing current adepts of developmental biology to observations and experiments that have lead their predecessors towards basic concepts still influential today.

Leading gender and science scholar Sarah S. Richardson charts the untold history of the idea that a woman's health and behavior during pregnancy can have long-term effects on her descendants' health and welfare. The idea that a woman may leave a biological trace on her gestating offspring has long been a commonplace folk intuition and a matter of scientific intrigue, but the form of that idea has changed dramatically over time. Beginning with the advent of modern genetics at the turn of the twentieth century, biomedical scientists dismissed any notion that a mother-except in cases of extreme deprivation or injury-could alter her offspring's traits. Consensus asserted that a child's fate was set by a combination of its genes and post-birth upbringing. Over the last fifty years, however, this consensus was dismantled, and today, research on the intrauterine environment and its effects on the fetus is emerging as a robust program of study in medicine, public health, psychology, evolutionary biology, and genomics. Collectively, these sciences argue that a woman's experiences, behaviors, and physiology can have life-altering effects on offspring development. Tracing a genealogy of ideas about heredity and maternal-fetal effects, this book offers a critical analysis of conceptual and ethical issues-in particular, the staggering implications for maternal well-being and reproductive autonomy-provoked by the striking rise of epigenetics and fetal origins science in postgenomic biology today.

Life As we Know It covers several aspects of Life, ranging from the prebiotic level, origin of life, evolution of prokaryotes to eukaryotes and finally to various affairs of human beings. Although Life is hard to define, one can characterize it and describe its features. The information presented here on the various phenomena of Life were all written by highly qualified authors including scientists, a professional athlete and three Nobel Laureates.

The final volume in this significant series, this publication mirrors the broad scientific attention given to ideas and issues associated with the life-span perspective: constancy and change in human development; opportunities for and constraints on plasticity in structure and function across life; the potential for intervention across the entire life course (and thus for the creation of an applied developmental science); individual differences (diversity) in life paths, in contexts (or the ecology) of human development, and in changing relations between people and contexts; interconnections and discontinuities across age levels and developmental periods; and the importance of integrating biological, psychological, social, cultural, and historical levels of organization in order to understand human development.

The overall scope of this new series will be to evolve an understanding of the genetic basis of (1) how early mesoderm commits to cells of a heart lineage that progressively and irreversibly assemble into a segmented, primary heart tube that can be remodeled into a four-chambered organ, and (2) how blood vessels are derived and assembled both in the heart and in the body. Our central aim is to establish a four-dimensional, spatiotemporal foundation for the heart and blood vessels that can be genetically dissected for function and mechanism. Since Robert DeHaan's seminal chapter "Morphogenesis of the Vertebrate Heart" pub lished in Organogenesis (Holt Reinhart & Winston, NY) in 1965, there have been surprisingly few books devoted to the subject of cardiovascular morphogenesis, despite the enormous growth of interest that occurred nationally and internationally. Most writings on the subject have been schol arly compilations of the proceedings of major national or international symposia or multiauthored volumes, often without a specific theme. What is missing are the unifying concepts that can make sense out of a burgeoning database of facts. The Editorial Board of this new series believes the time has come for a book series dedicated to cardiovascular morphogenesis that will serve not only as an important archival and didactic reference source for those who have recently come into the field but also as a guide to the evolution of a field that is clearly coming of age."

No field of contemporary biomedical science has been more revolutionized by the techniques of molecular biology than developmental biology. This is an outstanding concise introduction to developmental biology that takes a contemporary approach to describing the complex process that transforms an egg into an adult organism. The book features exceptionally clear two-color illustrations, and is designed for use in both undergraduate and graduate level courses. The book is especially noteworthy for its treatment of development in model organisms, whose contributions to developmental biology were recognized in the 1995 Nobel Prize for physiology and medicine.

It is appropriate at the outset of this book to pose a question that was often asked --of the organizers before the meeting took place and later among those who participated in the meeting -- "What is meant by 'Systems Approaches' in the study of developmental neurobiology?" The answer, as we originally conceived it, can be succinctly summarized by the word "interactions". That brief epithet was expanded during the general discussion portion of the meeting, where the following definition was offered: "Systems approaches in developmental neurobiology are unified by attention to the emergent properties of the developing system under investigation and by a focus on the aspects of development of the nervous system that depend on interactions among its various elements, be they molecular, intracellular or multicellular. " As opposed to ignoring complexity or trying to wish it away, those of us who utilize a systems approach embrace the principle that complexity is what makes the nervous system special. We have come to recognize that wherever we look, we find interactions which are to be probed and eventually. understood. Even the so-called "simple systems", a term that has been used to describe many invertebrate preparations, are embraced under the above definition, since with further study it is becoming increasing clear that such systems are not as simple as once thought. We also include molecular genetics under the systems rubric. After all, genes regulate other genes which regulate others, and so it goes.