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PubMed1978

Proliferative and degenerative events in the early development of chick dorsal root ganglia. I. Normal development.

Development of the chick dorsal root ganglia was examined in 4.5- to 9.5-day embryos. Tritiated thymidine (3H-TdR) and autoradiography was used to analyze proliferative activity and the Feulgen procedure to analyze degenerative activity in ganglia 12-17. Proliferative activity was found to be elevated through 4.5 days of incubation when as many as 14% of the ganglionic cells become labelled following a one-hour exposure to 3H-TdR. By 6.5 to 7.5 days proliferative activity decreases to 2-4% in the lateroventral (LV) regions and to approximately 1% in the mediodorsal (MD) regions of the ganglia. However, there appears to be increased proliferative activity by the end of the experimental period at 9.5 days. Birthdate studies demonstrate that large-scale neuronal production occurs between 4.5 and 6.5 days in the LV regions and between 4.5 and 7.5 days in the MD regions. After those times ganglionic proliferative activity must be largely nonneuronal in nature. This nonneuronal proliferation is greater in LV than in MD regions and in brachial than in nonbrachial ganglia. Degenerative activiy was found to be absent from the ganglia until after 4.5 days of incubation. It then increases rapidly, and by 5.5 days 5% of the LV cells in nonbrachial ganglia are degenerating. Degenerative activity then declines but is still present at 9.5 days. In contrast to results of an earlier study (Hamburger and Levi-Montalcini, '49), degenerative activity was also found in the LV region of brachial ganglia and the MD regions of brachial and nonbrachial ganglia. The pattern of LV degenerative activity in brachial ganglia is similar to that in nonbrachial ganglia, but the level of activity is lower. In the MD regions degenerative activity increases throughout the experimental period, and by 9.5 days as many as 4% of the MD cells are degenerating.

Age Factors↗

PubMed1978

Development of the diencephalon in the rat. II. Correlation of the embryonic development of the hypothalamus with the time of origin of its neurons.

The development of the nuclei of the hypothalamus was examined in normal and X-irradiated embryos from day 13 (E13) to the day before birth (E22). The diencephalic neuroepithelium was subdivided into three lobes (dorsal, medial, and ventral) and two lobules (superior and inferior). The hypothalamus is derived from the ventral lobe and the inferior lobule. The ventral neuroepithelial lobe generates the neurons of most of the early arising hypothalamic structures, including those of the lateral tier nuclei associated with the medial forebrain bundle, and the heterogeneous intermediate tier nuclei. A specialized neuroepithelial region lining the diamond shaped ventricle produces the early neurohypophysial magnocellular neurons; the neurons of the paraventricular nucleus remain at this site, whereas the neurons of the supraoptic nucleus could be traced migrating laterally. The neurons of the late arising hypophysiotropic area of the posterior hypothalamus are derived from components of the inferior neuroepithelial lobule: the dorsomedial and ventromedial nuclei apparently from a shared matrix in the main portion of the inferior lobule; the tuberomammillary-arcuate complex from its posteroventral recess. The triple-decked and sequentially produced components of the mammillary system may arise from separate neuroepithelial sites. The autoradiographic results of the previous study (Altman and Bayer, '78a) showed that the structural and functional heterogeneity of the mature hypothalamus is paralleled by cytogenetic heterochronicity; the present embryonic observations indicate that many of the distinguishable components of the hypothalamus arise from a mosaic of heterogeneous neuroepithelial sites.

Animals↗

PubMed1979

Development of the diencephalon in the rat. VI. Re-evaluation of the embryonic development of the thalamus on the basis of thymidine-radiographic datings.

The development of the thalamus was examined in normal and X-irradiated embryos from day 13 (E13) to the day before birth (E22). The differentiating, radioresistant neurons of the lateral habenular nucleus, derived from a portion of the superior neuroepithelial lobule (SL1), were settling by day E15 and by this time the habenulopeduncular tract was forming. The neurons of the reticular nucleus, derived from the middle neuroepithelial lobe, began to settle on day E15 but a massive migration was still evident on day E16. Adjacent to the reticular nucleus the internal capsule appeared on day E16; this fiber bundle seemed to be continuous with fibers embedded in the first transitory zone of cells issuing from the dorsal neuroepithelial lobe. Because of the immaturity of the neocortex at this time, it was postulated that thalamocortical fibers of the dorsal thalamus are the earliest components of the internal capsule. By day E17 all the sensory relay nuclei of the thalamus were recognizable and it was assumed that the second transitory zone issuing from the receding dorsal neuroepithelial lobe contained the neurons of the later forming intralaminar nuclei. Suggestive evidence was obtained that the late arising neurons of the medial thalamus (the anterior nuclei, the mediodorsal nucleus, and some or all of the midline nuclei) originate in a portion of the superior neuroepithelial lobule designated as SL2. Our present and previous studies showed that the major divisions of the hypothalamus and thalamus are derived embryonically from distinguishable parts of the third ventricle neuroepithelium. This implies the te third ventricle neuroepithelium has a "mosaic" organization and suggests that the fate of hypothalamic and thalamic neurons may be determined to some extent while their precursors are still proliferating.

Animals↗

PubMed1981

Organization and development of brain stem auditory nuclei of the chicken: dendritic development in N. laminaris.

Nucleus laminaris (NL) is a third-order auditory nucleus in the avian brain stem which receives spatially segregated binaural inputs from the second-order nuclei magnocellularis. The examination of the development of dendritic structure in NL revealed a number of events: In the initial period of dendritic growth (E 8--9) there is no gradient of dendritic morphology or apparent size. Starting about E 9--10, there is a spatiotemporal gradient of proliferation of numerous fine dendritic processes, from rostromedial to caudolateral, corresponding with the morphological lamination of NL, and possibly with the onset of cell death. This is followed by a spatiotemporal gradient of the elimination of the overproliferated processes, from rostromedial to caudolateral possibly coinciding with the cessation of cell death. A result of the spatiotemporal gradients of dendritic process proliferation and elimination is a spatial gradient in the morphology (extension, branching) of the remaining "mature" dendrites. At E 15 there is only a slight spatial gradient of total dendritic size across NL; this gradient is larger at E 19, and by P 25 there is a 13-fold change in dendritic size from rostromedial to caudolateral. Regression analyses suggest the size gradient begins to form when NL activity becomes driven by cochlear activity, at about E 14. The progressive formation of the size gradient is largely the result of two factors: the growth of dendritic trees, and the loss or primary dendrites. The growth rate of the dendritic trees of NL cells was found to be very highly correlated with the intensities of the sound frequencies to which the cells respond. From E 15 to P 25 there is a 50% loss of the "mature" primary dendrites of NL neurons. The separate dorsal and ventral dendritic size gradients seen at E 15 realign to coincide at E 19, and the moderate correlation of dorsal and ventral dendritic sizes seen at E 15 and E 19 is significantly increased at P 25, indicating a developmental process of sharpening in the relationship of the dorsal and ventral dendritic organizations in the nucleus. The data suggest that a key element in the regulation of dendritic size and structure in n. laminaris may be the activity of the afferents to the cells.

Aging↗

PubMed1985

Torpedo electromotor system development: neuronal cell death and electric organ development in the fourth branchial arch.

The fourth branchial arch of Torpedo marmorata has been examined at the light and electron microscopic level during development. Of interest was the determination of the extent of electric organ tissue reported to be present in this arch and its possible relationship to electromotoneuron cell death in the electric lobes. The main electric organ of the torpedo is derived from the hyoid and first three branchial arches and is innervated by four major electromotor nerves. Extensive electromotoneuron cell death occurs in the electric lobes and most notably in the posterior poles. This feature could be due to a tendency for these neurons to innervate the fourth branchial arch where little or no electric tissue is formed. Our findings support this conclusion but are not entirely consistent with the idea that a population mismatch has occurred. This is because cell death precedes the genesis of the target cells. The presence of innervated differentiated electric tissue in this arch is also reported, leading to the conclusion that Torpedo marmorata possesses an accessory electric organ.

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PubMed2005

Hearing in Drosophila: development of Johnston's organ and emerging parallels to vertebrate ear development.

In this review, I describe recent progress toward understanding the developmental genetics governing formation of the Drosophila auditory apparatus. The Drosophila auditory organ, Johnston's organ, is housed in the antenna. Intriguingly, key genes needed for specification or function of auditory cell types in the Drosophila antenna also are required for normal development or function of the vertebrate ear. These genes include distal-less, spalt and spalt-related, atonal, crinkled, nanchung and inactive, and prestin, and their vertebrate counterparts Dlx, spalt-like (sall), atonal homolog (ath), myosin VIIA, TRPV, and prestin, respectively. In addition, Drosophila auditory neurons recently were shown to serve actuating as well as transducing roles, much like their hair cell counterparts of the vertebrate cochlea. The emerging genetic and physiologic parallels have come as something of a surprise, because conventional wisdom holds that vertebrate and invertebrate hearing organs have separate evolutionary origins. The new findings raise the possibility that auditory organs are more ancient than previously thought and indicate that Drosophila is likely to be a powerful model system in which to gain insights regarding the etiologies of human deafness disorders.

Animals↗

PubMed1981

Analysis of mesenchyme in the developing hind limb of Rana pipiens larvae with implications for neural development.

Mesenchyme in the hind limbs of Rana pipiens tadpoles may serve as an important influence on the development of specific neural structures involved in limb innervation. Thus a histological quantification of mesenchyme was undertaken to identify landmark stages with respect to mesenchyme presence and neural events. Mesenchyme remained as a high percentage of the limb tissue until stage V (Taylor-Kollros stages, '46), after which it declined dramatically until its virtual absence after stage XI. The volume of mesenchyme, however, was greatest at stages VIII-IX. Periods of high and low mesenchyme content were correlated in time with potential limb involvement in regulating limb innervation and motor neuron loss from the lateral motor columns. This provides additional evidence for developmental relationships between events of the limb and neural tissues.

Animals↗

PubMed1987

Development of the glycogen body of the Japanese quail, Coturnix japonica. I. Light microscopy of early development.

The glycogen body is a functionally enigmatic structure located in lumbosacral region of the spinal cord in birds. This tissue is unique to birds, and, although it is believed to be present in all species, studies on the glycogen body to date have been confined largely to the domestic chicken. The present study is the first to describe the glycogen body of the Japanese quail (Coturnix japonica) during incubation and at hatching. Light microscopy and histochemistry were used to identify the glycogen body in the spinal cord of the developing quail beginning at 7 days of incubation and to ascertain the presence of nerve fibers in that tissue at hatching.

Animals↗

PubMed1993

A comparison of the development of neuropeptide and MAP2 immunocytochemical labeling in the macaque visual cortex during pre- and postnatal development.

The appearance of Substance P (SP) and Neuropeptide Y (NPY) has been studied using light microscopic immunocytochemical labeling throughout the complete developmental span of Macaca nemestrina monkey striate cortex. In the adult, 80% of the NPY+ neurons occur in the white matter (WM) and most of the remainder are medium to large multipolar neurons in layer 2. Fibers occur in all layers except 4C and are very numerous, given the relatively small number of NPY+ cell bodies. NPY+ neurons first were seen at embryonic day (E) 75. Most neurons were in the intermediate zone (IZ), but a few were in the immature cortical plate (CP). An adult-like distribution was present by E125 for neurons and by birth for fibers, but fiber staining intensity and number increased to postnatal year 1 (P1yr). In adult cortex, numerous SP+ nonpyramidal neurons were present in layers 2-6 and WM, but SP+ fibers were surprisingly infrequent. During development, significant numbers of SP+ neurons were not seen in the CP until E113-125. Later prenatal ages had a prominent plexus of SP+ cell bodies and fibers at the layer 5/6 border. This plexus disappeared by P12wk due to either down-regulation of SP or cell death. SP+ neurons in IZ/WM were very sparse until birth after which they increased in number and staining intensity up to P1yr, suggesting a postnatal up-regulation of SP in a preexisting WM subpopulation. Cell densities were determined for SP, NPY, and the neuron-specific marker microtubule-associated protein 2 (MAP2) to clarify the developmental dynamics of IZ/WM neurons. MAP2+ cell densities in WM peaked around birth and then declined 20% in the outer half and 77% in the inner half of WM. SP+ cell density rose 57% from birth to P20wk and then declined 20% into adulthood. NPY+ cell density was fairly constant prenatally and then rose 300% by adulthood. Neuropeptide cell density changes took place predominantly in the outer WM. These data indicate that cell death does occur in the general population of monkey striate cortical WM neurons. In contrast, both SP+ and NPY+ cells are characterized by minimal cell death and a late expression of neuropeptides which causes an increase in neuropeptide+ cell density in postnatal WM.

Animals↗

PubMed1975

Studies of the development of congenital anomalies in rats. III. Effects of inhibition of mitochondrial energy systems on embryonic development.

Pregnant rats were treated with various inhibitors of mitochondrial oxidative energy metabolism and with lowered oxygen tension, and the embryo fetuses examined for the occurrence of congenital malformations and for changes in enzymatic activities. Treatment with all agents tested resulted in the production of skeletal anomalies. Sodium phenobarbital was the most teratogenic of the drugs tested and produced a high incidence of malformations which included cleft palate, tail anomalies, spinal retroflexion, domed head, and facial hypoplasia. Diphenylhydantoin produced a low incidence of syndactyly and oligodactyly. In addition to its effects on fetal growth and development chloramphenicol appeared to interfere with implantation. Tissue preparations from embryos exposed to sodium phenobarbital and chloramphenicol showed markedly lowered levels of DPNH oxidase activity. Cytochrome oxidase activity was also markedly lowered in the preparations from chloramphenicol-exposed embryos. Enzyme activities in preparations from embryos exposed to malonate and diphenylhydantoin appeared unaffected, although the drugs are strong inhibitors of electron transport in vitro; the lack of apparent effect may be due to the fact that both drugs do not bind to the enzyme preparations and were diluted 100- to 200-fold during preparation and assay of the tissue homogenates.

Abnormalities, Drug-Induced↗

PubMed1995

Larval spicules, cilia, and symmetry as remnants of indirect development in the direct developing sea urchin Heliocidaris erythrogramma.

Nonfeeding larvae of the echinoid Heliocidaris erythrogramma were raised in culture and examined for expression of a larval skeleton and for the arrangement of the ciliated band. Opaque larvae were fixed, cleared, and examined under polarized light for evidence of calcification. By 35 hr after fertilization (at 22 degrees C), a pair of triradiate spicules was present at the posterior end of the larvae. Each member of this pair formed a fenestrated spicule as it grew laterally. This pair and another pair which formed subsequently, were arranged across a plane of bilateral symmetry orthagonal to the juvenile oral aboral axis. These paired larval spicules can be identified as reduced expressions of postoral and posterodorsal rods found in plutei, and their expression indicates that the juvenile rudiment of H. erythrogramma forms on the left side and that larval body axes are conserved in this modified larva. By 44 hr the ciliated band formed as an incomplete transverse loop of three segments at the posterior end and on the dorsal surface of the ovoid larva. Cilia in these segments grew to lengths of 45-50 microns, longer than other swimming and feeding cilia reported for echinoderm larvae. Band segments are interpreted as expressions of epaulettes (specialized swimming bands) rather than the feeding ciliated band of the pluteus. The ciliated band segments and the larval spicules are both bilaterally symmetrical with respect to the same plane and indicate conserved larval bilateral symmetry despite the major asymmetry of the fates of cells on either side of this plane in their contribution to juvenile development.

Animals↗

PubMed1993

Glial cell line-derived neurotrophic factor is expressed in the developing but not adult striatum and stimulates developing dopamine neurons in vivo.

The potential role of glial cell line-derived neurotrophic factor (GDNF) as a trophic molecule for midbrain dopamine neurons was examined using two different approaches: in situ hybridization and intraocular transplantation. The presence of mRNA for GDNF was noted in striatal and ventral limbic dopaminergic target areas in the developing (E20-P7) rat, but not the adult rat. Signals were also found in nondopaminergic areas during maturation, such as the cerebellar anlage, spinal cord, and thalamus. Lesions of the nigrostriatal pathway in neonatal or adult rats, using 6-hydroxydopamine injected into the medial forebrain bundle, did not elicit upregulation of mRNA for GDNF. Grafts of fetal ventral mesencephalon in the anterior eye chamber were exposed to repeated injections of GDNF, which elicited a marked and dose-dependent increase in transplant volume. A low (0.1 microgram/eye) and high (1 microgram/eye) dose of GDNF both led to a somewhat larger mean area of dopamine fiber outgrowth into host irides. In the transplants, cell counts of tyrosine hydroxylase (TH)-immunoreactive neurons revealed a doubling of cell numbers in the low-dose group and about four times as many cells in the high-GDNF-dose group compared to controls. Moreover, the density of TH-immunoreactive nerve fibers was markedly and significantly higher in transplants treated with the high GDNF dose. Since the volumes of these transplants were also larger, the total amount of both TH-positive cells and TH-positive nerve fibers was many-fold greater in the high-GDNF group than that in the controls. Taken together, these data support the concept that GDNF functions as a dopaminotrophic factor in vivo.

Aging↗

PubMed2001

Taurolidine improves survival by abrogating the accelerated development and proliferation of solid tumors and development of organ metastases from circulating tumor cells released following surgery.

BACKGROUND: Surgical trauma is partly responsible for enhancing tumor growth through a variety of mechanisms that are still not fully elucidated. The use of perioperative immunostimulants may modulate these effects. This study examined the effect of administration of taurolidine after laparotomy or laparoscopy on the growth of solid tumor, the establishment of hepatic and lung metastases, and effects on natural killer (NK) and lymphokine-activated killer (LAK) cell function. METHODS: B16 melanoma right flank tumors were established in mice (n = 180). These animals underwent anesthesia only (control) or laparotomy or laparoscopy (n = 60 per group) and were randomized to receive either saline or taurolidine (n = 30 per group) at specific time points. Survival was determined in each group, and in a further 90 mice tumor growth was followed over 10 days postoperatively. The experiment was repeated in 540 mice, which underwent one of the three procedures and were treated with either saline or taurolidine. NK and LAK cell cytotoxicity (NKCC, LAKCC) was determined at several time points postoperatively. In a further experiment, B16 melanoma tumor cells were delivered via tail vein injection (n = 180) and intrasplenic injection (n = 180). The effect of saline or taurolidine administration on survival after the establishment of metastases was determined, and again in a further 180 mice the establishment of metastatic deposits in the liver or lungs was determined after 8 days. RESULTS: Survival appeared to be significantly decreased in both the solid-tumor model and the metastatic models undergoing laparotomy compared to laparoscopy and controls (P < 0.0001) and to a lesser extent in the laparoscopy group compared to controls (P < 0.001). Flank tumor growth and metastatic tumor formation were more significant in laparotomy groups compared to laparoscopy groups and controls, but also to a lesser extent in laparoscopy groups compared to controls (P </= 0.05). NKCC and LAKCC were significantly decreased in the same patterns (P < or = 0.03). However, treatment with taurolidine abolished these effects, restoring NKCC and LAKCC (P < or = 0.04) and laparoscopy groups (P < or = 0.001). CONCLUSION: It appears that changes that occur after the trauma of laparotomy, and to a lesser extent, after laparoscopy, significantly enhance the growth of primary tumors as well as the development of metastases from circulating tumor cells and are associated with a suppression of host antitumor surveillance mechanisms. This not only affected tumor progression in the immediate postoperative period, but also ultimately affected survival. Taurolidine, a known immunostimulant, appears to abrogate the effects of surgical trauma on primary and metastatic tumor growth and also enhances survival. This may have significant value in the management of tumor-bearing patients undergoing resection.

Animals↗

PubMed1983

Ontogenetic development of the pineal organ, parapineal organ, and retina of the three-spined stickleback, Gasterosteus aculeatus L. (Teleostei). Development of photoreceptors.

The ontogenetic developments of the pineal organ, parapineal organ, and retina were studied by the use of light and electron microscopy in embryos and fry of the teleost, Gasterosteus aculeatus, from 60 to 168 h after fertilization. Sixty to 66 h after fertilization, the primordium of the pineal complex is discernible in the diencephalic roofplate; the parapineal anlage is located rostral to the pineal anlage. Photoreceptor cells endowed with outer segments are present in the embryonic pineal organ already after 72 h, whereas outer segments of retinal photoreceptors could not be demonstrated before 144 h (hatching occurs between 120-144 h). Furthermore, neuropil formations with synaptic specializations are present in the rostral part of the pineal organ 108 h after fertilization. At 72 h, the embryonic parapineal parenchyma is already differentiated into parapinealocytes, which give rise to the parapineal tract, and glia-resembling elements. Although parapinealocytes carry cilia (9 X 2 + 0), only a single outer segment of the photoreceptor type could be demonstrated in the parapineal organ of one adult stickleback. Photoreceptors present in the pineal organ of unhatched embryos are hardly involved in visual functions, but may already at this early developmental stage serve as photoneuroendocrine transducers.

Animals↗

PubMed1986

Development of myofibrils in the gizzard of chicken embryos. Intracellular distribution of structural proteins and development of contractility.

The intracellular distributions of major muscle proteins, myosin, actin, tropomyosin, alpha-actinin, and desmin, in smooth muscle cells of chicken gizzard at various stages of embryogenesis were investigated by immunofluorescence-labeling of enzyme-dispersed cells cultured up to three hours. These muscle proteins, except some part of myosin, were organized into fibrous structures as soon as synthesis and accumulation of proteins started. As for myosin, a considerable amount of it was dispersed in soluble cytoplasm as well. On the other hand, Ca++-dependent contractility was detected with detergent-extracted myoblasts and glycerinated tissue from embryos older than 7 days. Although the nascent myofibrils bear a resemblance to "stress fibers," the former could be distinguished from the latter by their high stability in dispersed, spherical cells. The above findings, therefore, show that the synthesis of contractile proteins is followed by immediate assembly of them into functional myofibrils without undergoing any intermediate structure. Based on these findings, the mechanism of myofibril formation in developing smooth muscle cells is discussed.

Animals↗

PubMed1976

A comparison of the proteins found in developing wild type larvae and developing lethal mutant larvae of Drosophila melanogaster.

Extracts of late larval lethal mutants were compared with extracts of wild type larvae of the same developmental age on double diffusion plates using 16 different antisera. Nearly all of the mutant extracts showed relative antigen concentration differences compared with the wild type and four of the mutants lacked a protein at death found in the wild type of the same developmental age. In each case it was a different protein. The results are discussed by considering the different ways in which mutations can lead to the loss of a protein in developing systems.

Animals↗

PubMed1989

Early development of the representation of the body surface in SI cortex barrel field in neonatal rats as demonstrated with peanut agglutinin binding: evidence for differential development within the rattunculus.

Physiological studies have demonstrated a highly organized somatotopic representation of the body surface in SI cortex of rat. This representation is correlated morphologically with the presence of barrel-shaped structures in layer IV. Conventional staining techniques reveal barrels in the latter part of the first postnatal week. Recently, the peroxidase conjugates of lectins, which recognize glycosylated molecules, have been used to study barrel field formation. Con A, for example, has been shown to bind primarily to prospective barrel sides and septa as early as postnatal day 3 (PND-3) in mouse. To date, investigations of SI cortex using the lectin (Arachis hypogaea) peanut agglutinin (PNA) have been confined to the study of the barrel field representation of the face and mystacial vibrissae in the mouse. In the present study we extend these findings to the development of the representation of the entire body surface called the rattunculus. Rats ranging from PND-1 (first 24 h after birth) to PND-12 were anesthetized with Nembutal and perfused with 4% paraformaldehyde and 2% glutaraldehyde in 0.2 M sodium cacodylate buffer. Brains were removed, flattened tangentially, and sectioned on a vibratome at 30-120 microns. Sections were blocked in TRIS-buffered saline (TBS) plus 2% bovine serum albumin and incubated in peanut lectin at 4 degrees C. Following incubation, sections were washed with TBS and processed using peroxidase histochemistry. Lectin binding in the prospective forelimb representation was apparent by PND-5 whereas lectin binding to the prospective face-mystacial vibrissae representation occurred before PND-4. These results suggest that body part representations show individual variations during early pattern formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1978

On the development of the cerebellum of the trout, Salmo gairdneri. II. Early development.

The early histogenesis of the cerebellum of Salmo gairdneri RICHARDSON, 1836 has been studied in fish ranging in length from about 5 to 14 mm, both with light microscopical and electron microscopical techniques. Structurally, the matrix cells correspond to those of other vertebrates. Mitoses occur predominantly at the ventricular surface, but peripheral mitoses are found as well, particularly in the period of highest mitotic activity. Mantle cell somata can be distinguished from the elongated matrix cells on the basis of their rounded shape. The neurogenetic and gliogenetic periods overlap considerably. Presumably the first mantle cells are all neuroblasts: as soon as the mantle layer starts to form, axonal profiles are found. In a slightly later stage glial differentiation is manifest in the radial processes contacting the meningeal surface. In young stages a distinction between neuroblasts and glioblasts can only be made on the basis of the structure of their processes. Processes of glioblasts can be distinguished from axons and dendrites by their paucity of microtubules. Dendrites, appearing in late-embryonic stages, contain the same organelles as axons, but in larger amounts. The first differentiation of mantle cell somata is an increase of rough endoplasmic reticulum, and that to a lesser degree in glioblasts than in neuroblasts. Neuronal nuclei are rounded and more electronlucent than those of mantle cells. Apart from zonulae adhaerentes between the internal processes of matrix cells, puncta adhaerentia occur frequently in the cerebellar anlage. However, they rarely occur on young neuron;. The possible significance of these junctions is discussed. The present study indicates that growth cones and filopodia are characteristic of most and probably of all types of cells in the early developing cerebellum. Growth cones contain much vesicular and tubular endoplasmic reticulum and in filopodia a fine filamentous network is present. In the somata of mantle cells growth areas were found, i.e. areas under the cell membrane with a similar content as growth cones. It is suggested that these areas anticipate the outgrowth of a new process.

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