At present, we do not fully understand at what stage of the evolution of living matter the first traces of defense reactions occurred. We even do not fully understand how and why immune systems reached their contem porary state in advanced vertebrates and man. It may be expected that in the near future these questions will be answered by comparative and develop mental biology. Together with an extraordinary explosion of our knowledge about immunity of mammals including man, an increase in the interests concerning origin and development of immune mechanisms at lower stages of the phylogeny can be observed. The search for simple types of immune mechanisms in less complex but still evolutionary successful animals is promising and may contribute to better understanding of highly complex immune adaptive responses in mammals. It is important to note that comparative and evolutionary immunology differs greatly from other branches of biomedical science. Apart from immunology and molecular biology, a specialist in this discipline has to be familiar with every detail of taxonomy, comparative anatomy, physiology, embryology, and even with the phyletic relationships of animals. Probably no monography could deal with the entire animal kingdom, because, in many cases, the insights into questions about immune mecha nisms of many animal groupings or phyla, and their possible evolutionary implications, are unknown or just now beginning to take shape. For the moment, our knowledge on such matters relies upon reconstructions of ideas that we have deduced from studies on members of relative taxa."

Human reproduction is the most dynamic of processes. The events which lead to the birth of a normal healthy infant have their origin long before actual fertilization. Indeed, the whole process can be looked upon as a continuum. Human fertilization and early development, once sequestered in the protective environment of the fallopian tubes and uterus, have now been exposed in the laboratory. These events have, over time, been extensively observed and catalogued in animal models. The tools of modem morphology and molecular biology have reopened issues long since considered settled as facets of early reproduction are reexplored. This volume, consisting of the proceedings of a workshop on uterine and embryonic factors in early pregnancy, has been designed to enhance that effort. Attention is focused largely on early embryonal development with special attention to the interrelationship between the embryo and the uterus in early pregnancy. Each of the contributing scientists brings with him or her the perspective of one specific discipline or another. The common denominator is the application of emerging techniques in modem molecular biology to problems pertaining to embryonal-uterine interaction. The goal is to consider specific areas of concern in a multidisciplinary way and to reexplore the factors behind early development and implantation. Uterine complement, the function of uterine macrophages immunoregulatory loops in the peri-implantation period, colony stimulating factors and interferon-like factors are reviewed and their interrelationship explored. Uterine angiogenesis factors as well as embryonic growth factors are also considered.

Pharmacokinetic variability of contraceptive steroids is a relatively under-explored area of contraceptive research, and hardly a common point of discussion among those who plan and deliver family planning services. Nevertheless, numerous independent studies over the last 15 years have indicated that women in different regions of the world vary in their pharmacokinetic response to contraceptive steroids. The causes of such variability are not known, but it has important consequences for contraceptive effectiveness. It may also offer insight to the basis of contraceptive side-effects. The impetus for this volume was to collect documentation of pharmacokinetic variability of contraceptive steroids, and to explore both the possible causes and implications of these data. Factors known to affect steroid pharmacokinetics, such as concurrent use of specific medications, are reviewed by Back and Orme. Other factors known to affect endogenous steroid dynamics are presented in chapters by Bradlow, Longcope, Goldin and Snow, because of their possible role in contraceptive steroid pharmacokinetics.

It is nearly a decade since the first Male Mediated Developmental Toxicity conference was held in Pittsburgh. The continuing public/scientific interest, growing amounts of animal data, introduction of innovative technologies, and increasing quantity of human epidemiological studies all suggest that male-mediated developmental toxicity is of major concern. A number of researchers concluded that a Second International Confer- ence on Male Mediated Developmental Toxicity was necessary. The ensuing volume is particularly timely because it impacts on areas of special emphasis in many countries, with respect to children's and reproductive health, as well as to basic molecular mecha- nisms of environmental insult, and genetic susceptibility and predisposition. The Programme and Local Organizing Committee, composed of Barbara Hales (Chair, McGill University), BernardRobaire (McGill University), Daniel G. Cyr (INRS/ Armand Frappier), Jacquetta M. Trasler (McGill University), Andrew F. Olshan (Uni- versity of North Carolina), Sally Perreault Damey (US EPA), Donald R. Mattison (March of Dimes), and Jan M. Friedman (University of British Columbia), spent over two years identifying individuals who had made key contributions in this field over the past decade and planning various aspects of the meeting. The meeting was held in Montreal in June 2001. A total of 132 persons, coming from five continents and representing some 18countries, took an active role in the proceedings. The conference was considered by all attendees to be a rousing success. Important discussions were held in the four break-out sessions, with a preliminary set of recommendations for action being presented by each panel.

''A valuable resource for those concerned with experimental teratology and risk assessment and those requiring general information about the causes of birth defects. The treatment of these issues is sophisticated, succinct, and logical.'' --- American Scientist, from a review of a previous volume The current volume covers intergenerational factors in pregnancy outcome, the thresholds for developmental toxicants, and four other subjects.

This is the third meeting we have organized which has explored the meaning of fetal neural developmental disruption in the etiology of schiwphrenia. The first was sponsored by the Schiwphrenia Research Branch with the scientific cooperation of Dr. David Shore. We met in Washington; the output of the meeting was published in a book entitled, Fetal Neural Development and Adult Schizophrenia. Cambridge University Press. 1991. The next meeting was an Advanced Research Workshop sponsored by NATO and was held at n Ciocco. Castelvecchio Pascoli. This meeting was reported in a NATO volume. Developmental Neuropathology of Schizophrenia and was edited by Mednick. Cannon. Barr and La Fosse. The current meeting has noted several advances in the field. There are additional psychiatric illnesses which have been found to be related to maternal viral infection in the second trimester. There have been studies reported which have definitely observed a viral infection in the mothers of fetuses who later evidenced schirophrenia. More evidence has been published which has replicated the "second-trimester effect." In the future studies will be wise to provide serological evidence of a viral infection and information on the precise viruses involved. Another important step will be to determine whether second-trimester maternal viral infection is related to a behavioral deficit in the infant. If neural development has been compromised. it might be possible to detect deficits in the infant with the proper measures. We look forward to future meetings at which these new areas might be explored.

~he major theme of this book is the development of the vertebrate central nervous system. ~is volume contains summaries of most of the invited participants at the NA~ advanced study institute entitled "Development of central nervous system in vertebrates" held in Maratea, Italy, from June 23-July 5, 1991. In order to address this topic, we have drawn upon a selection of current studies dealing with molecular, cellular and system analysis which specifically pertain to the general principles of the development. ~he major aim of this institute was to bring together a select group of investigators who would present their views on the current issues in their respective fields and to foster extensive discussions amongst participants in smaller groups. Such interactions brought together the exchanges of ideas amongst participants and helped clarify the intricate details and formulate new vistas and collaborations. Since the study of nervous system development has focused mostly on the origin of neuron and glia cells, the area of current research was represented by talks on early cellular events including effects of growth factors, BOX and other gene expressions and cell lineage of specific cell type(s). Formation of specific cell types and the specific neuronal connections have been a major theme in the study of the nervous system development. Recent technical advances has resulted in new information at both cellular and molecular levels which have provided new details. Current research was represented by "selective" topics discussed at the meeting.

This volume reports the proceedings of a NATO Advanced Workshop held in Castelvecchio Pas coli, Italy, from August 28 - September 1, 1989. An important inspiration for this Workshop came from our studies in Helsinki and Denmark, which have found that exposure to an influenza epidemic during the second trimester of fetal development increases the risk of adult schizophrenia. This finding has stimulated an important new hypothesis in the study of the etiology of schizophrenia. It has suggested the possiblity that disturbances of brain development during gestation may contribute to the risk of adult schizophrenia. We determined that it would be of value to bring together schizophrenia researchers and those doing basic studies of the development of the brain. Both groups of researchers were encouraged to communicate at a level that would help other scientists to integrate their knowledge and techniques into their own discipline. For this reason, perhaps, the papers of this volume are remarkably clear and not difficult to understand. The first four chapters describe the neurochemical and structural aspects of brain development. The chapter by Dziegielewska and Saunders discusses transport mechanisms and the properties of endogenous and exogenous substances that control the internal environment of the developing brain. In the second chapter, Nowakowski reports on his studies of the develop ment of the hippocampus in mice genetically inbred to exhibit disruptions of neural migration.

This book launches a new continuing series in developmental biology. Any new publishing venture in science can only be justified if it satisfies a need and fulfills that need in an exemplary way. I believe that there is an acute need for comprehensive treatises on specialized topics in developmental biology-especially because this is a very diverse field that receives con tributions from a wide variety of disciplines. It is difficult to remain abreast of progress in multifaceted topics and to understand how the various aspects of a topic interrelate. The volumes that will comprise this series are designed to facilitate those processes. Each volume of this series will attempt to convey the current status of research and thought on a specific topic in development, place current research within historical perspective, and lay the intellectual groundwork for future research. These volumes are intended to provide an in-depth background on these topics for advanced undergraduates, graduate stu dents, and senior scientists. An investigator considering research in one of these areas will get an overview of the field as well as discover the status of recent research in the area."

Leo Buss expounds a general theory of development through a simple hierarchical extension of the synthetic theory of evolution. He perceives innovations in development to have evolved in ancestral organisms where the germ line was not closed to genetic variation arising during the course of ontogeny.

Originally published in 1988.

The Princeton Legacy Library uses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These paperback editions preserve the original texts of these important books while presenting them in durable paperback editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905.

Thanks to enormous scientific efforts of the last decades, in vitro fertilization (IVF) and in vitro production (IVP) have now been introduced successfully in the practice of human infertility treatment and cattle breeding programs. This comprehensive book allows us to bridge the knowledge from both biomedical and veterinary fields of research. For the first time, studies concerning the human embryo as well as embryos from domestic species are brought together. The central theme of the book is "the assessment of mammalian embryo quality." In 15 chapters, written by well-known scientists, different aspects of the assessment of mammalian embryo quality are summarized. Non-invasive and invasive techniques to evaluate embryo quality are separated in two parts. In addition the book is provided with appendices on practical aspects and, thus, the book should be present in each laboratory for IVF and IVP.

The survival of the human species has improved significantly in modern times. During the last century, the mean survival of human populations in developed countries has increased more than during the preceding 5000 years. This improvement in survival was accompanied by an increase in the number of active years. In other words, the increase in mean life span was accompanied by an increase in health span. This is now accentuated by progress in medicine reducing the impact of physiologic events such as menopause and of patho logical processes such as atherosclerosis. Up to now, research on aging, whether theoretical or experimental, has not contributed to improvement in human survival. Actually, there is a striking contrast between these significant modifications in survival and the present knowledge of the mechanisms of human aging. Revealed by this state of affairs are the profound disagreements between gerontologists in regard to the way oflooking at the aging process. The definition of aging itself is difficult to begin with because of the variability of how it occurs in different organisms."

Dictyostelia are soil amoebae capable of extraordinary feats of survival, motility, chemotaxis, and development. Characterised by their ability to transform from a single-celled organism into an elaborate assemblage of thousands of synchronously-moving cells, Dictyostelids are often referred to as 'social amoebae', and have been the subjects of serious study since the 1930s. Research in this area has been instrumental in understanding many problems in cellular biology. Beginning with the history of Dictyostelids and discussing each stage of their development, this book considers the evolution of this unique organism, analyses the special properties of the Dictyostelid genome, and presents in detail the methods available, at the time of the book's original publication in 2001, to manipulate their genes. Representing the synthesis of such material and with an emphasis on combining classical experiments with modern molecular findings, this book will be essential for researchers and graduates in developmental and cellular biology.

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 morpho genesis, despite the enormous growth of interest that occurred nationally and inter nationally. Most writings on the subject have been scholarly compilations of the proceedings of major national or international symposia or multi authored volumes, without a specific theme. What is missing are the unifying concepts that can often 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 mor not only as an important archival and didactic reference phogenesis that will serve source for those who have recently come into the field but also as a guide to the evo lution of a field that is clearly coming of age.

From a review of an earlier volume: 'Both the experimental and the human aspects of teratology are presented in this comprehensive text by a stellar group of internationally recognized scientists and clinicians....A valuable resource for those concerned with experimental teratology and risk assessment and those requiring general information about the causes of birth defects. The treatment of these issues is sophisticated, succinct, and logical.'-American Scientist

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.

Of the three organizers of this NATO Advanced Research Workshop on "Neocortex: Onto geny and Phylogeny," one derived most of his knowledge about neocortex from studies on birds, another had never studied any animal but the cat and could probably recognize not more than ten animal species, and the third had very limited experience with mountaineering. They had in common the belief that evolutionary thinking permeates what biologists do, but that evolution of species and structures cannot be directly experimentally addressed. Although the fossil record can provide some major insights, the inroad to the evolution of the brain is indirect, via comparative anatomy and developmental biology. By identifying similarities and differences between brain structures in the species at hand, comparative anatomy generates hypotheses of evolutionary transformations. By understanding the rules of morphological transformation, developmental biology can, in principle, estimate the likelihood that a given transformation may have actually occurred. The meeting was a way to check if this notion is viable, by gathering together scientists from these two fields. Standing, left to right: F. Ebner, V. Caviness, M. Weisskopf, B. Fritszch, N. Swindale, J. Walter, H. Karten, J. Pettigrew, E. Welker, M. Cynader, D. Frost, L. Lopez-Mascaraque, P. Katz, H. Jerison, E. Soriano, Mayor of Alagna, Dr. G. Guglielmina, and associate, H. Van der Loos, B. Finlay, H. Scheich, C. Ruela. Seated: S. Pallas, T. Lohmann, J. De Carlos, F. Valverde, G. Innocenti, M. Diamond v "Gathering" does not accurately describe what really happened."

This series was established to create comprehensive treatises on specialized topics in developmental biology. Such volumes are especially vital in develop mental biology, since it is a very diverse field that receives contributions from a wide variety of disciplines. This series is a meeting-ground for the various practitioners of this science, facilitating an integration of heterogeneous infor mation on. specific topics. Each volume is intended to provide the conceptual basis for a comprehen sive understanding of its topic as well as an analysis of the key experiments upon which that understanding is based. The specialist in any aspect of devel opmental biology should understand the experimental background of the field and be able to place that body of information in context to ascertain where additional research would be fruitful. At that point, the creative process takes over, and new experiments are designed. This series is intended to be a vital link in that ongoing process of learning and discovery. If it facilitates schol arship, it will serve an important function."

The cerebral neo cortex, unique to mammals, is regarded as the prerequisite for higher cognitive function and is the structure most closely associated with the idea of the "mind" . Expansion of mental capa city between mammals is most typically associated with an evolutionary increase in neocortical volume that culminates in the intricately folded configuration of sulci and gyri so charac teristic of the primate cerebral cortex. Yet, the basic unit structure and funda mental connectivity of cortex appears to have been preserved from the smooth cortex of the mouse or rat to the highly convoluted cortical mantle of the human that, if stretched out as a sheet, would be large enough to wrap the entire human brain multiple times. The basic similarity in structure and func tion has made it possible to conduct studies in the relatively simple cortices of rat or mouse and have the results pertain to the understanding of the primate, including human, cortex. The neo cortex is an intriguing structure for the study of cell differentiation. Its dozens of neuronal cell types and small handful of different glial types have their origin in a pseudostratified germinal epithelium lining the ventricular surface of the forebrain. In its mature form, neocortex is a six-Iayered struc ture; five of its layers contain multiple different but characteristic neuronal types with the sixth occupied by neuronal processes. Various glial cells are dis persed throughout all six layers.

1 Kevin Moses It is now 25 years since the study of the development of the compound eye in Drosophila really began with a classic paper (Ready et al. 1976). In 1864, August Weismann published a monograph on the development of Diptera and included some beautiful drawings of the developing imaginal discs (Weismann 1864). One of these is the first description of the third instar eye disc in which Weismann drew a vertical line separating a posterior domain that included a regular pattern of clustered cells from an anterior domain without such a pattern. Weismann suggested that these clusters were the precursors of the adult ommatidia and that the line marks the anterior edge of the eye. In his first suggestion he was absolutely correct - in his second he was wrong. The vertical line shown was not the anterior edge of the eye, but the anterior edge of a moving wave of patterning and cell type specification that 112 years later (1976) Ready, Hansen and Benzer would name the "morphogenetic furrow". While it is too late to hear from August Weismann, it is a particular pleasure to be able to include a chapter in this Volume from the first author of that 1976 paper: Don Ready! These past 25 years have seen an astonishing explosion in the study of the fly eye (see Fig.

Indonesia possesses the second largest primate population in the world, with over 33 different primate species. Although Brazil possesses more primate species, Indonesia outranks it in terms of its diversity of primates, ranging from prosimians (slow lorises and tarsiers), to a multitude of Old World Monkey species (macaques, langurs, proboscis moneys) to lesser apes (siamangs, gibbons) and great apes (orangutans). The primates of Indonesia are distributed throughout the archipelago. Partly in response to the number of primates distributed throughout the Indonesian archipelago, Indonesia is classified as the home of two biodiversity hotspots (Wallacea and Sundaland). In order to be classified as a hotspot, an area must have a large proportion of endemic species coupled with a high degree of threat including having lost more than 70% of its original habitat. Two areas within Indonesia meet these criteria. The tremendous diversity of primates in Indonesia, in conjunction with the conservation issues facing the primates of this region, created a need for this volume.

The NATO Advanced Study Institute on "Experimental Embryology in Aquatic Plant and Animal Organisms" was attended by more than 70 participants, including 15 invited main lecturers from 18 different countries. In accordance with the main purpose of the meeting, senior scientists, postdoctoral investigators and graduate students working in areas of descriptive and experimental embryology, classical, molecular and developmental biology, physiology and biochemistry etc. , were brought together for two weeks as a community with a strong common interest in "development"; that is, the multiple phenomena and mechanisms, in molecular, cellular, genetic and organismic terms, observed in the development of aquatic organisms. Initial concern that the great variety of biological models as well as of research subjects would harm the scientific quality and coherency of the course was unnecessary. It was exactly this breadth which made the Institute worthwhile for each of the participants. Since many of the "students" were younger scientists starting a career, it was the main goal of the course to offer a concise overview of selected system models of primarily aquatic organisms and to present and discuss research carried out in the past and in progress. Thus, each main speaker gave two in-depth lectures: one in which he presented an overview of "his" model and another dealing with current investigations.

This book evolved through the efforts of several organizations and the dedication of many individuals. In 1987, we received arequest to propose a workshop topic for the Fifth International Theriological Congress (ITC) to be held in August 1989 in Rome, Italy. After looking up the meaning of the word "theriological" in the dictionary and discovering that it pertains to mammalian behavior, we decided a symposium on sensory abilities of whales and dOlphins would be an interesting topic. The ITC convenes only every five years and has the distinction of being very weIl attended by scientists from around the world. We thought that hosting a workshop in conjunction with the ITC would attract a variety of international scientists that rarely have the opportunity to interact. Fortunately for all involved, our prediction was correct. The first two days of the workshop, 23-24 August 1989, were held in conjunction with ITC and the nearly 1,000 attending scientists were able to view our posters and listen to lectures. The third day was limited to only ab out 65 invited scientists who were divided into topical working groups chaired by a rapporteur.

This book focuses on the intersection between cell cycle regulation and embryo development. Specific modifications of the canonical cell cycle occur throughout the whole period of development and are adapted to fulfil functions coded by the developmental program. Deciphering these adaptations is essential to comprehending how living organisms develop. The aim of this book is to review the best-known modifications and adaptations of the cell cycle during development. The first chapters cover the general problems of how the cell cycle evolves, while consecutive chapters guide readers through the plethora of such phenomena. The book closes with a description of specific changes in the cell cycle of neurons in the senescent human brain. Taken together, the chapters present a panorama of species - from worms to humans - and of developmental stages - from unfertilized oocyte to aged adult.

Interest in sexuality and reproductive function does not cease when people begin to age. Instead, a new set of questions arises. Women want to know if it is safe to have babies in their late thirties and early forties. They want to know more about hot flashes and other symptoms of menopause-which ones are dangerous and which are merely uncomfortable. They are eager to learn about the relative risks and benefits of estrogen replacement therapy. Men, too, are concerned about age-related changes in their sexual function. Experts in reproductive physiology, gerontology, and genetics met at the National Institutes of Health in June of 1984 to discuss these and other concerns about aging and the reproductive system. The conference on Aging, Reproduc tion, and the Climacteric was sponsored by the American Fertility Society, The National Institute on Aging, and the National Institute of Child Health and Human Development. This volume is based on the proceedings of that confer ence."