In many aspects hematopoiesis in newborn rodents, especially in rats, resembles hema- topoiesis in the human fetus in the 6th-7th month of gestation. In man the transition from the stage of liver to bone marrow erythropoiesis takes place at this time (Bessis, 1973). In rodents, however, the liver is almost the only place where hematopoiesis occurs until birth. Thereafter it is replaced to a growing extent by the bone marrow, which so far consists mainly of immature mesenchymal cells (Maximow, 1910; Cuda, 1970). Thus hematopoietic precursor cells appear in the sternum only around 30 h after birth. Just as in premature human infants, a macrocytic anemia can be demonstrat- ed in normal neonatal rats (Lucarelli et aI., 1964, 1968). Beside liver (fetal) and bone marrow, the spleen is involved in hematopoiesis. In rodents like rats and mice, splenic hematopoiesis persists more or less markedly until adulthood; in man, however, it ceases after birth and reappears only under certain pathological conditions (Fischer et aI., 1970; Hennekeuser et aI., 1967; Fresen, 1960).

The octapeptide angiotensin II (ANG II, Fig. 1) is the key effector substance of the renin-angiotensin system (RAS) (Werning 1972, Page and Bumpus 1974, Hierholzer 1977, Vecsei et al. 1978, Johnson and Anderson 1980 lit. ). ANG II is formed in two enzymatic steps. Renin acts on renin substrate, a glycoprotein, to produce angiotensin I (ANG I, a decapeptide), which in turn is acted upon by converting enzyme to form ANG II (Skeggs et al. 1968, Fig. 1). Renin substrate (angiotensinogen) is produced mainly in the liver (Page et al. 1941) and is a constituent of the ~-globulin fraction in the circulating plasma (Plentl et al. 1943). The two enzymes involved in the formation of ANG II from renin substra- te are formed at various sites in the body. Renin (E. C. 3. 4. 99. 19) is produced mainly in the granular epithelioid cells of the kidney (Cook 1971, Taugner et al. 1979, Davi- doff and Schiebler 1981), and converting enzyme (CE, E. C. 3. 4. 15. 1) occurs chiefly in the lung (Ng and Vane 1967, Bakhle 1974 lit. ) as well as in numerous other tissues, such as the juxtaglomerular apparatus of the kidney (Granger et al. 1969, 1972) and the brush border of the renal proximal tubule (Ward et al. 1975, 1976; Ward und Erdos 1977). The biological effects of ANG II are numerous.

The aim of this investigation is threefold: (a) to determine the time of origin of neurons of the rat cranial nerve ganglia; (b) to reexamine the embryonic development of the cranial nerve ganglia in the light ofthese dating results; and (c) to attempt to relate the chronology of these peripheral events to developmental events in those nuclei of the medulla that are intimately associated with the cranial nerve ganglia. Although thymidine-radiography has been used for over 2 decades to investigate the time of origin of neurons, most of these studies dealt with central nervous struc tures. There are relatively few studies available concerning the birth dates of neurons in the peripheral nervous system. In fact, to our knowledge, there is only a single thymidine-radiographic report available dealing with the time of origin of neurons of a cranial nerve ganglion in a mammal; this is the recent study by Forbes and Welt (1981) of neurogenesis in the trigeminal ganglion of the rat. In the present study we determined the birth dates of neurons of the trigeminal, facial, vestibular, "glosso pharyngeal, and vagal ganglia of the rat. We utilized the progressively delayed com prehensive labeling procedure, a method which, in contrast to the single-pulse labeling procedure, allows the exact quantification of the proportion of neurons formed on a particular day."

In 1949, the Dutch anatomist Jan Boeke was able to write: "The socalled interstitial cells . . . which lie at the end of the sympathetic endformation as a connecting link between the nervous endformation and the effector cells, are . . . shown to be of pri mary importance for the transferring and the remoulding of the nervous stimulus . . . . " And: " . . . the problem of the interstitial cells and of the synapse is the most impor tant problem of neurohistology of the future. " When Boeke wrote this, he advocated the generalized concept, holding that inter stitial cells were intercalated between autonomic nerves and effector cells. A frank illus tration of this is presented by Tinel (l937), who places interstitial cells of Cajal (ICC) as terminal neurons of all autonomic nerves (his Fig. 1). While there have been over 100 light microscopic investigations (Table 1) of ICC in tissues and organs other than intestine, none of these have been followed up by electron microscopic studies. It is important to bear in mind that when the term ICC is used today, the only reference tissue for which sufficient information (i. e., including an ultrastructural identification) on the ICC is at hand is the intestine, or rather the muscularis externa of small inte stine (in Table 1, those contributions which relate to intestinal ICC are underlined)."

Of all the classes in the animal kingdom, birds represent the best known. There are in total about 8600 living species, and the systematic study of this class is more or less complete. Extensive observations - to a large extent by amateur ornithologists - with respect to geographical distribution, life cycles, demands on and adaptations to the environment, breeding habits, migration, and so forth have contributed towards basic and more widely relevant knowledge, e. g., in the areas of ethology, ecology, and evo lution and also in social biology (Hilprecht 1970; Farner and King 1971). Together, all these aspects are affected by the reproductive biology of birds, and studies have therefore been carried out for many years with special emphasis on this subject. How ever, until now this emphasis in avian reproductive biology has been physiological and in particular endocrinological (Murton and Westwood 1977; Roosen-Runge 1977). The morphology of the gonads has been treated in far less detail, and has been confined to a comparatively small number of species, compared with other classes of vertebrates. Reproduction is the section in the life cycle of an animal which is most dependent upon environmental conditions. Reproduction therefore usually takes place at a par ticular time, when stress for the adult animals is at its lowest and the chances of sur vival for the newborn are at their highest, i. e."

Over the past few decades an exceedingly large number of experimental and clinical investigations have been performed in an attempt to analyze the way in which the kidney functions. The basis for all this work was established during the nineteenth and the early twentieth century by morphologists (Bowman 1842; Hyrtl1863, 1872; Heidenhain 1874; Peter 1909; von Mollendorf 1930). All these investigators clearly outlined the extremely heterogeneous assembly of renal tissue and also defined the nephron as the smallest morphological unit. It was further the merit of these anato- mists and histologists to preclude quite a number of nephron functions based merely on their careful observations. Contemporary histologists have been able to add little to these observations. Unfortunately with the introduction of physiologic in vivo et situ studies on kidneys the interest in heterogeneity waned. This lack of attention was aggravated by the introduction of the clearance techniques which cannot account for regional differences in the function of the smallest unit, the nephron. That ana- tomic heterogeneity has a functional correlate was strongly suggested by Trueta et al. (1947) and vigorously stimulated a number of studies. The development of physiologic microtechniques, like micropuncture and microperfusion of single nephrons, or the perfusion of isolated nephron portions and electrophysiologic studies, enormously expanded our knowledge concerning details regarding nephron and total renal func- tion.

The present monograph is an imaginative and courageous attempt to provide a synthesis of knowledge concerning the af- ferent connections of the medial basal hypothalamus. Only somebody who has lived through most of the explosive develop- ment - over the last 25 years or so - in the neuroscience in general, and in hypothalamic functional neuroanatomy in parti- cular, can fully appreciate the remarkably consistent picture emerging from this study. The writer of this foreword was (alas!) an active participant in the very early and premature, and also largely naive, attempts to penetrate the "jungle" of hypothalamic connections with degeneration methods when they first became available in the late 1930s. (I have told a part of this rather pathetic story is an autobiographical sketch in Pioneers in Neuroendocrinology [Meites et aI. , (eds) (1975), Vol I. Plenum] because I was sufficiently self-critical not to publish my early results. ) Even with the suppressive Nauta-type silver stains, introduced in the mid-1950s, studies of hypothala- mic connections had only marginal results, which the reader will certainly appreciate if he compares the relevant figures in the first edition of Hypothalamic Control of the Anterior Pituitary [Szentagothai et al. (1962) Akademiai Kiad6, Budapest], with Dr. Zaborszky's concluding diagrams. The approach used by Dr. Zaborszky of combining the more advanced Fink-Heimer type degeneration techniques, and some of their most recent modifications by Gallyas et al.

The mature vertebrate retina is a highly complicated array of several kinds of cells, capable of receiving light impulses, transforming them into neuronal membrane currents, and transmitting these in a meaningful way to central processing. Before it starts to develop, it is a small sheet of unconspicuous cells, which do not differ from other cells of the central nervous system. The chain of events which lead to the trans formation from this stage into that of highly specialized cells ready to fulfll a specific task, is usually called "differentiation. " Originally, this word indicated firstly the proc ess of divergence from other cells which were previously alike, and secondly, the change from an earlier stage of the same cello lt has become widespread practice to imply by the word "differentiation" also the acquisition of specific properties and capacities which are characteristic of a mature, Le. , specifically active, cello Every cell is active at any stage of development, but certain activities are shared by most cells (e. g. , the activities of preparing and accomplishing proliferation, that of initiating development, that of maintaining a certain level of metabolism), while there are others which are shared by only a small number of - originally relate- cells. In most cases these latter activities are acquired by the fmal steps of cellular development, the terminal "differentiation. " In the context of the present paper, the word "function" will refer to this latter type of specific activity.

Biopsy pathology of the lymphoreticular system has been written primarily for diagnostic histopathologists although we hope that other workers in the field of lymphoreticular disease will find it of interest and value. With our primary readership in mind we have generously illustrated most sections of the book. Allillustrationsare of haematoxylin and eosin stained sections unless otherwise specified. Conceptual understanding of the histogenesis and interrelationship of non-Hodgkin's Iymphomas has been in a state of turmoil for over a decade. In more recent years immunological and immunocytochemical studies have clarified some problems although in other areas such as the T-celllymphomas histogenetic interrelationships are still far from clear. We are aware, therefore, that in writing this book we have been aiming at a moving target; nevertheless, we feel that the need for such a book, particularly amongst diagnostic histopathologists, outweighs the advan tage of waiting until all the t's are crossed and all the i's dotted."

The 7th edition includes changes reflecting modern understanding, terminology and teaching of the musculoskeletal system. There are changes on 42 different pages including many new or enhanced notes on function and 20 new descriptions or explanations of anatomical relationships. All muscle illustrations are new.

Anthropocentricity and pragmatism seem to be the main reasons why pigeons have served as the "black boxes" of so many psychologists and neurobehaviorists during the past decade. Anthropocentricity, because at first glance pigeons show several strik ing features which bear a beautiful similarity to human systems in respects such as drinking, bipedality, territoriality, and apparently easy pursual of individual interests. Pragmatism, because of the suspected lesser complexity of the pigeon's system, which enables them to serve as good paradigms for human systems. For example, the visually guided grasping system of the beak could be used as a model for the visually guided grasping system of the tips of the thumb and forefinger in humans (personal communi cation, Zeigler). Other pragmatic reasons are the low cost of breeding these birds, their easy adaptation to experimental conditions, and their obvious capacity for learning and remembering. Although a closer and more critical examination largely undermines the anthropomorphic arguments, this has not diminished interest in the pigeon. In many studies on sensorimotor and motivational processes of hunger, thirst, and learning, pecking and drinking behavior serve as the systems on which the outcome of different black box systems is measured. Clear examples of this application are found in McFarland (1964, 1965), Dawkins (1966), Dawkins and Dawkins (1973), Goodman and Schein (1974), Machliss (1977), and Zeigler, Levitt, and Levine (1980)."

In the past decennia nonhuman primates have been increasingly used for research purposes in various scientific fields. Much interest has been focused on this group of animals in general and on the rhesus monkey in particular because of its close phylo genetic relationship with man. In some fields of research, however, such as embryology and microscopic anatomy, much less attention has been paid to nonhuman primates, probably because of the expense involved in the collection of the extensive material needed. On the other hand, teratological and experimental embryologic studies must be based upon a thorough knowledge of the normal ontogenesis since only in that way can a reliable distinction be made between normal and abnormal or induced develop ment. Each ontogenetic study essentially consists of a comparison of different deve lopmental stages. In most reports dealing with the development of individual organs or their subunits the material used is classified according to the estimated age or the length of the embryos. These criteria, however, are not valid, since considerable varia tion in developmental stage occurs between animals of the same age even between littermates and between animals of the same length. Therefore a method is needed for assigning embryos to successive developmental stages that are defmed on the basis of extemal and internal characteristics. This type of classification was elaborated by Stree ter (1942, 1945, 1948,1951), who arranged human embryos into developmental hori zons numbered XI through XXIII."

In recent years the inferior olive and its projection to the cerebellum have attracted considerable interest. Numerous experimental anatomic and electrophysiologic studies have been undertaken, and much new information has been brought forward. Many apparently discordant observations have been reported however, and on many points the data obtained by the use of different methbds and approaches appear to be diffi cult to reconcile. Much of the interest in the olivocerebellar projection concerns the topographical localization within the projection. Particularly as a result of research in recent years the pattern of localization has turned out to be far more complex than previously be lieved. It was found useful, therefore, to attempt a review of the subject in the hope that a critical analysis of available observations might make it possible to obtain an integrated picture of the olivocerebellar projection and perhaps fmd some basic principles in the organization of this fiber system. As will be seen, our attempt has been only partly successful. There are still riddles that remain to be solved. In the present review attention will be focused on problems related to the locali zation within the olivocerebellar projection, particularly its anatomic aspects. An extensive review of the physiology of the inferior olive has been published recently by Armstrong (1974), who considers some anatomicophysiologic correlations as well. Physiologic fmdings will be referred to here mainly in relation to our main theme."

The afferent connections of the cerebellar cortex of the cat have been extensively in- vestigated by Alf Brodal and his collaborators using retrograde degeneration methods. These experiments (reviewed in Larsell and Jansen 1972) established that cerebellar corti- cal afferents arise from widespread areas of the brain stem and spinal cord. Brain stem nuclei shown to provide input to the cerebellar cortex included the pontine nuclei, the medial and descending vestibular nuclei, vestibular cell group x, the lateral reticular nucleus, the perihypoglossal nuclei, the paramedian reticular nucleus, the inferior olive, and the external cuneate nucleus. In addition, the red nucleus and certain of the raphe nuclei were thought to send fibers to the intracerebellar nuclei, but not to the cortex. With the advent of the horseradish peroxidase (HRP) technique, new information on the distribution and organization of cerebellar cortical afferents has recently be- come available. Thus Gould and Graybiel (1976) demonstrated that afferents to the cat cerebellar cortex arise from a previously undescribed lateral tegmental cell group at the level of the isthmus and from the intracerebellar nuclei, as well as from the classic precerebellar nuclei. Moreover, these studies showed that fibers from the vestibular nuclei, previously thought to be distributed only to the flocculonodular lobe and uvula, reach widespread areas of the cerebellar cortex. Experiments by other investi- gators have established that the cerebellar cortex of the cat receives afferents from cer- tain of the raphe nuclei (Shinnar et al. 1975; Taber Pierce et al.

Studies on cell kinetics in untreated animals have for the most part been done on or gans in which many proliferating cells can be found. In general the proliferating cells have been identified either in histologic sections as mitoses or by autoradiography as labeled interphase cells following the injection of a labeled precursor of DNA, such as 3H_ or 14C-thymidine (TdR). A great many proliferating cells can be observed in the rat and mouse brain during the embryonic period and for a short time after birth, and many studies on cell kinetics have been performed for this phase of life. By contrast, very few proliferating cells are found in the brain of adult rodents (except for the subependymallayer, see below). As a result, only isolated studies have been done on cell kinetics during this period. Al though there is an increase in proliferating cells in adult animals which had been pre treated (e g. , by wounding, X-irradiation, viral infection, withdrawal of water), this proliferation too has not been investigated in detail. A number of studies have been done since 1959 on the proliferation of cells in the sub ependymal layer of the lateral ventricles of the forebrain. This cell type is well suited for such investigations because mitoses can be found there even in animals which are quite old. Since the studies ofLe blond and co-workers (Walker and Leblond 1958 ;Messier et al.

References ............................... 76 Subject Index ............................. 93 VIII Acknowledgments This study was funded by the Deutsche Forschungsgemeinschaft. I am indebted to Prof. Dr. W. Schlote for helpful advice and numerous discussions. I am also grateful to Dr. G. Kurz-Isler for her generous help in problems dealing with electron microscopy and to Mrs. B. Sabrowski for her careful preparation of the manuscript. The careful translation of T.C. Telger is gratefully acknowledged. The translation was financially supported by the Erwin Riesch Foundation. IX 1 Introduction One of the basic principles underlying the efficiency and adaptability of cellular meta bolism is the structural compartmentalization of the cell. Only through compartmenta lization can reaction components be kept apart prior to their reaction, isolated from other "reaction spaces" during the course of their reaction, and the reaction products incorporated into designated structures or transported to remote parts of the cell. Thus, the partitioning of the cellular substance into countless membranous spaces corresponds to the spatial segregation of reaction components, and the dynamics of intracellular membrane systems is an expression of ever-changing equilibrium condi tions and the continuous formation of new reaction spaces. It has been shown with some certainty that many of the processes in membrane dynamics can take place only with the aid of contractile proteins such as actin, myosin, and tubulin."

The earliest mention of a cell sheath enveloping the body of the neurons in sensory ganglia is probably the following description by Valentin: "Sowohl die Kugeln der Be- legungsformation 1 , als die Primitivfasem, werden von eigenthi. imlichen, sie isolirenden Scheiden umgeben, welche aile Stufen der Dicke von einer fast gar nicht mehr wahr- nehrnbaren Zartheit bis zu einer ziemlich bedeutenden Starke durchlaufen. Diese Hill- len sind aber immer zellgewebeartiger Natur" (1836, p 162). In some illustrations of the above mentioned paper the nuclei of the satellite cells adjacent to the surface of the nerve cell body, both in the trigeminal ganglion and in the ganglia of the vegeta- tive nervous system, are clearly shown (Fig. lA). The author, however, miSinterpreted these nuclei as pigment granules (Pigmentkorperchen). A little later, Remak (1838) denied the existence of the perineuronal cell sheath. This prompted a ready reply from Valentin (1839), who offered a more detailed description of the perineuronal cell sheath, illustrated it with new drawings (Fig. IB), and gave a correct interpreta- tion of the nuclei. In fact, he wrote: Fig. lA-B. Nerve cell bodies of sympathetic ganglia with the nuclei of the satellite cells on the neuronal surface. Redrawn from Valentin; A, 1836; B, 1839.

A vascular system consists of a supplying arterial and a draining venous part which are connected by a terminal vascular network. The arterial segment can be characterized according to the structural features of the vessel wall. However, it is sometimes diffi- cult to distinguish the capillary from the postcapillary vessels on the basis of structural features alone. On the other hand, physiologic qualities such as permeability can hard- ly be associated with an equivalent histologic pattern of the vessel wall (lllig 1961; Rhodin 1967, 1968; Hauck 1971; Westergaard 1974). A defmition of a vascular seg- ment based on biologic significance should combine morphological and functional qualities of the vessel walls. During the ontogeny of the mammalian organism a variety of vascular patterns (e. g. , distribution of arteries and veins, arrangement of the capillaries) has been formed typical of each organ (Wolff et al. 1975; Baez 1977). The capillaries connect the feed- ing arterioles and the collecting venules in two different ways according to the branch- ing pattern of the terminal vessels (Hauck 1975, Wolff et al. , 1975). The arterioles and venules are directly connected by capillary segments. Consequently a terminal vessel called arteriovenous (a-v) capillary results, or a closely meshed capillary network is de- veloped which connects arterioles and venules by a variable number of small capillary branches arranged parallel to the preexisting a-v capillary.

Wilhelm His, one of the founders of developmental neurobiology, was convinced "that the processes of generation and development obey fundamental and simple laws and submit to the general laws of nature" (His 1901). Therefore, we should be able to find immediate conditions, dependencies and rules determining the de velopment of an organic form. With this in mind, His (1874) defined the task of embryology as follows: "Developmental biology is essentially a physiological science; it has not only to describe how each individual form develops from the egg, it has to derive this development in such a way that each developmental stage together with all its specialities appears as a necessary consequence of the immediately pre ceding stage . . . Only if developmental biology has given a perfect physiological deriva tion for any given form, has it the right to say that it has explained this individual form. " The ultimate aim of a physiological derivation would be that laws of growth valid for organic ,beings can be expressed as mathematical formulae (His 1874). To exemplify this, he formulated a universal and purely formal law of growth in mathematical terms making the comment: "I now suggest that the body form follows immediately from germinal growth and can be derived from the given germinal form according to the laws of growth. My interest is, therefore, firstly to detect the law of growth empirically and secondly to derive consecutive forms of the developing or ganism by applying this law.

Anatomy to most people is a subject which suggests the cutting up of dead bodies (the word literally means cutting up). In addition it is generally known that Vesalius published a book in 1543 in which much of the human body was described in detail and more or less accurately. A subject which is dead and ancient fre quently has little appeal especially if it appears to involve learning a large amount of factual information. For many years anatomy has had to struggle with these disadvantages and at times one has had the impression that there is almost a conspiracy on the part of everyone to suggest that anatomy is unnecessary. There is no doubt, however that a knowledge of the structures of the body, for that is what anatomy is, whether it is what can be seen with the naked eye or with different kinds of microscope, is an essential preliminary and corollary to the understanding of the functions of the body. It was no historical accident that Vesalius, the anatomist, preceded Harvey, the physiologist. No apology need be made for trying to present the basic facts of anatomy to anyone interested in the human body and to members of any profession which will have to cope with the physical and mental problems of children, men and women in health and in sickness. It is not intended that the reader should know every thing contained in this book."

This volume is based on presentations by the world-renowned investigators who gathered at the 74th annual Cold Spring Harbor Symposium on Quantitative Biology to celebrate the 150th anniversary of the publication of Charles Darwin's On the Origin of Species. It reviews the latest advances in research into evolution, focusing on the molecular bases for evolutionary change. The topics covered include the appearance of the first genetic material, the origins of cellular life, evolution and development, selection and adaptation, and genome evolution. Human origins, cognition, and cultural evolution are also covered, along with social interactions. The line-up of speakers comprised a stellar list of preeminent scientists and thinkers such as the zoologist and prolific author E. O. Wilson (Harvard University); Jack W. Szostak (Harvard Medical School), a 2009 Nobel Prize winner who studies the chemistry of life's origins; and Nobel Prize winner and former president of HHMI Thomas Cech (Colorado Institute for Molecular Biotechnology), to name just a few.