Biomedical subjects

R S Nowakowski

Publications and source records attributed to R S Nowakowski.

At least 55 records · Page 3Linked to original sources

PubMed1994

Morphology and distribution of astrocytes in the molecular layer of the dentate gyrus in NZB/BlNJ, Dreher, and C57BL/6J mice.

Numerous ectopic granule cells are found in the molecular layer of the dentate gyrus in NZB/BlNJ and dreher mutant mice. These ectopic neurons occur either singly or in small clusters. In contrast, few ectopic granule cells are seen in the dentate molecular layer of C57BL/6J mice and dreher control littermates. In this investigation we have examined the morphology, number, and distribution of molecular layer astrocytes in NZB/BlNJ, dreher homozygotes, dreher littermate controls, and C57BL/6J mice to determine the effect of the presence of ectopic granule cells. In the molecular layer of C57BL/6J mice and dreher control littermates, astrocytes have a typical stellate appearance with processes emanating in all directions. The arborization of astrocytes in areas devoid of ectopic granule cells in NZB/BlNJ mice and dreher homozygotes was similar to that in C57BL/6J mice and dreher control littermates. In contrast, the morphology of astrocytes in the immediate vicinity of ectopic granule cells or ectopic clusters was distinctly non-stellate. Furthermore, the somata and processes of these astrocytes occasionally appeared to make intimate contact with the ectopic granule cells. A quantitative analysis of the number and distribution of astrocytes in NZB/BlNJ vs C57BL/6J mice and dreher vs. control littermates indicated that these parameters were not altered by the presence of the ectopic neurons. We conclude that the trophic effects of ectopic neurons on glial cells can affect the growth and orientation of astrocytic processes without a concomitant effect on glial cell number.

Animals↗

PubMed1993

Abnormal distribution of acetylcholinesterase activity in the hippocampal formation of the dreher mutant mouse.

The distribution of acetylcholinesterase(AChE) in the hippocampal formation of the dreher mutant mouse was studied by comparing homozygous mutant (drsst-J/drsst-J) with littermate control (+/? or +/+). In the control mice, AChE activity was most intense in the inner one-third of the stratum oriens and lacnosum of the hippocampus, and in the inner one-fifth of the molecular layer of the dentate gyrus. In contrast, in homozygous dreher mice, AChE activity in area CA3c of the hippocampus was not restricted to the stratum oriens, and extended upward into the infrapyramidal and suprapyramidal mossy fiber layers, the lower part of the stratum radiatum, the pyramidal cell layer, and downward toward the alveus. In addition, the distribution of AChE activity was modified by accompanying with ectopic pyramidal cells or with disruption of the pyramidal cell layer. AChE activity in the dentate gyrus of the dreher mouse was not confined to the inner one-fifth of the molecular layer. These findings indicated that the cholinergic input to the hippocampal formation is not normal in the dreher mutant mouse. Since the areas of AChE activity correspond to the presence of ectopic pyramidal cells in the dreher mouse, incoming cholinergic fibers may form synapses with these ectopic cells and with the dendrites of normal pyramidal cells that extend into the expanded area of AChE activity.

Acetylcholinesterase↗

PubMed1993

Cell cycle parameters and patterns of nuclear movement in the neocortical proliferative zone of the fetal mouse.

Cytogenesis is the critical determinant of the total number of neurons that contribute to the formation of the cerebral cortex and the rate at which the cells are produced. Two distinct cell populations constitute the proliferative population, a pseudostratified ventricular epithelium (PVE) lying within the ventricular zone (VZ) at the margin of the ventricle, and a secondary proliferative population that is intermixed with the PVE within the VZ but also is distributed through the overlying subventricular and intermediate zones of the cerebral wall. The present analysis, based upon cumulative S-phase labeling of the proliferative cells with 5-bromo-2'-deoxyuridine, is principally concerned with the PVE of the gestational-day-14 (E14) murine cerebral wall. It has immediate but also more far reaching general objectives. The most immediate objective, essential to the design and interpretation of later experiments, is to provide estimates of critical parameters of cytogenesis for the PVE. The growth fraction is virtually 100%. The lengths of the overall cell cycle, S-, G2+M-m, and G1-phases are 15.1 hr, 3.8 hr, 2 hr, and 9.3 hr, respectively. The PVE is homogeneous with respect to cell cycle length. For methodological considerations, these estimates are more accurate than estimates of the same parameters obtained in earlier analyses based upon S-phase labeling with tritiated thymidine. It is particularly with respect to a shorter length of S-phase determined here that the present values are different from those obtained with thymidine. At a more innovative level, the temporal and spatial resolution of nuclear movement made possible by the methods developed here will allow, in a way not previously attempted, a fine-grained tracking of nuclear movement as cells execute the successive stages of the cell cycle or exit the cycle subsequent to mitosis. Such observations are pertinent to our understanding of the regulatory mechanisms of neocortical histogenesis and the cell biological mechanisms that govern the proliferative cycle of the ventricular epithelium itself. It is known that the velocity of nuclear movement in the PVE is maximum in G2 (fourfold increase from S-phase) and minimum in M and early G1.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Cytoarchitectonic abnormalities in hippocampal formation and cerebellum of dreher mutant mouse.

The laminated structures in the hippocampal formation and cerebellum of homozygous dreher mice were compared to their littermates and to C57BL/6J mice in Nissl- and myelin-stained preparations. In the dreher dentate gyrus, ectopic granule cells were situated in the molecular layer, and frequently there was either partial or complete absence of the infrapyramidal limb of the granule cell layer. In the dreher hippocampus, the cells of the pyramidal cell layer in area CA3 formed widely dispersed arrangements, and there were ectopically situated pyramidal cells in the stratum radiatum and stratum oriens. In the dreher cerebellum, 3 abnormal patterns were observed: (1) disruptions of foliation with normal cytoarchitectonic structure, (2) foliation with a mixture of normal laminated structure and abnormal laminated structure, and (3) almost complete absence of the cerebellum. In abnormal folia exhibiting the second or third pattern, islands consisting of agglomerations of both granule cells and Purkinje cells or just granule cells were observed. The neuronal heterotopias and cytoarchitectonic disorganization observed in the present study are apparently secondary to disruption of cell proliferation and neuronal migration produced directly or indirectly by the dreher mutation. In addition, the fact that the phenotypic abnormalities in homozygous dreher mice produces different abnormal morphologies in different specimens may be useful for analyzing the development of the hippocampal formation and cerebellum.

Animals↗

PubMed1992

Competitive interactions during dendritic growth: a simple stochastic growth algorithm.

A simple growth algorithm is presented that deals with one feature of dendritic growth, the distance between branches. The fundamental assumption of our growth algorithm is that the lengths of dendritic segments are determined by the branching characteristics of the growing neurite. Realistic-appearing dendritic trees are produced by computer simulations in which it is assumed that: (1) growth of individual neurons occurs only at the tips of each growing neurite; (2) the growing neurite can either branch (as a bifurcation) or continue to elongate; (3) events at any one growing tip do not affect the events at any other growing tip; and (4) the probability of branching is a function only of the distance grown either from the cell body (if branching has not occurred) or from the previous branch point. An analytic solution of a differential equation based on these same assumptions produces a distribution of dendritic segment lengths that accurately fits an experimentally determined distribution of dendritic segment lengths of reconstructed neurons, accounting for about 89% of the sample variance. Our analysis indicates that, immediately following branching, the temporary suppression of further branching during dendritic growth may be an important mechanism for regulating the distance between branches.

Algorithms↗

PubMed1992

BUdR as an S-phase marker for quantitative studies of cytokinetic behaviour in the murine cerebral ventricular zone.

BUdR incorporation into replicating DNA, detected immunohistochemically, is used as an S-phase marker in the proliferative cell populations of the cerebral wall of the mouse embryo on the 14th gestational day (E14). The analysis initiates a series of studies concerned with the cytokinetic behaviour and cell output of proliferative populations involved in neocortical histogenesis. On E14 there are two periventricular proliferative zones in the cerebral wall. These are the ventricular and subventricular zones. The ventricular zone is a pseudostratified epithelium. DNA replication occurs with the cell nucleus in the outer zone of the epithelium and mitoses at the ventricular surface. Prior applications of BUdR for studies of cytogenesis in the CNS have been extended in two principal ways: (1) basic fuchsin was used as counterstain for BUdR-negative nuclei and (2) labelling indices were determined separately in strata or bins, 10 microns in height, through the full depth of the ventricular zone and overlying cerebral wall. It was established that a single injection of 50 micrograms g-1 into the pregnant dam was associated with labelling of 100% of nuclei in S-phase over an interval extending from 15 min to at least 2.0 h after injection. The zone where nuclei are undergoing S-phase (S-phase zone) extends through the outer four bins of the ventricular zone. The method has high quantitative reproducibility with an SE for labelling indices in bins within the S-phase zone less than 10% of the average values. Evidence is provided that BUdR incorporation is initiated with the nucleus in the outer aspect of the S-phase zone. The efficiency of incorporation of the marker is reduced as nuclei near the end of DNA replication and move to the inner aspect of the S-phase zone.

Animals↗

PubMed1991

Abnormalities of foliation and neuronal position in the cerebellum of NZB/BINJ mouse.

To analyze developmental abnormalities related to neural migration in the NZB/BINJ mouse, the pattern of cerebellar foliation and neural position were compared with that of a normal mouse (C57BL/6J). Three abnormalities of cerebellar foliation--(1) lobe isolated from other cerebellar lobes, (2) lobes imbalanced in relative amounts or ratio of granular cell layer and molecular layer, (3) lobes in which some Purkinje cells and the molecular layer was embedded in the granular cell layer--were observed in NZB/BINJ mice. These morphological abnormalities were not limited to a specific lobe. On the other hand, abnormalities of neural position were observed in both granule and Purkinje cells. The pattern of ectopically-situated granule cells, in general, could be divided into 3 types: (1) large cell clusters extending from granular cell layer to the pia mater or middle part of the molecular layer, (2) clusters of various sizes scattered within the white matter and (3) clusters formed by combination of granule cells extending from two opposed granular cell layers to the molecular layer. The pattern of ectopically-situated Purkinje cells could be divided into 4 types: (1) ectopia of a group of cells from one part of the Purkinje cell layer, (2) ectopia of a single Purkinje cell observed in the molecular layer, (3) single Purkinje cell scattered within the white matter accompanied by clusters of ectopic granule cells and (4) ectopic Purkinje cells embedded in the granular cell layer. The abnormalities in position of both granule cells and Purkinje cells was not limited to a particular cerebellar lobe.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Glial cell differentiation in neuron-free and neuron-rich regions. I. Selective appearance of S-100 protein in radial glial cells of the hippocampal fimbria in human fetuses.

The proliferative cells of the developing hippocampal fiber tract fimbria have only the potential for gliogenesis; thus the developing fimbria provides an ideal model for the study of the development and differentiation of its constituent glial cells. In the first stage of development, the fimbrial primordium can be distinguished morphologically, and during the second stage, the fimbria becomes a well-defined fiber tract. In the third stage, a divergent immunocytochemical staining pattern clearly demarcates the neuron-free fimbria from the hippocampus, where a mixed neuro- and gliogenesis occurs. The distinct expression of S-100 protein in radial glial cells is restricted to the fimbria. During the final stage of development, the ventricular lining of the fimbria will mature into an ependyma. It is suggested that the S-100-positive radial glial cells of the fimbria, which probably retain their proliferative capacity, represent a homogeneous population of precursor cells that will give rise to the glial cells of the adult fimbria. The appearance of S-100 in the fimbrial radial glial cells seems to occur coincidentally with the establishment of hippocampal commissural connections. The S-100-positive radial glial cells of the fimbria may guide and segregate populations of growing axons by providing physical and chemical cues. Thus, S-100 protein per se seems to be intimately involved in modulation and regulation of axonal growth and patterning.

Axons↗

PubMed1991

Glial cell differentiation in neuron-free and neuron-rich regions. II. Early appearance of S-100 protein positive astrocytes in human fetal hippocampus.

The development of the human fetal hippocampus and dentate gyrus has been studied immunocytochemically. The first glial cells to appear are vimentin-positive radial glial cells. A gradual transition from vimentin to glial fibrillary acidic protein (GFAP) reactivity in the radial glial cells occurs at week 8. The GFAP-positive radial glial cells transform into astrocytes from week 14. A population of small S-100-positive somata which morphologically and spatially are distinct from GFAP-positive radial glial cells and their transformed progeny, are found as early as week 9.5 in the hippocampus during the period of peak neurogenesis. The well-defined immunoreactivity of the morphologically homogenous cell subpopulation for S-100 protein, which has been used as an astrocytic marker in the adult hippocampus, indicates that astrocytes may differentiate at very early gestational ages in human fetuses. The S-100-positive astrocytes are thought to be derived from ventricular zone cells, which at the time of their appearance do not express any of the applied astrocytic markers (S-100, GFAP, vimentin). It is suggested that the S-100-positive astrocytic cell population interacts with the first incoming projection fibers, so modulating the pattern of connectivity.

Astrocytes↗

PubMed1991

Left out axons make men right: a hypothesis for the origin of handedness and functional asymmetry.

The origin and underlying mechanisms of hand preference are still unresolved, despite extensive research and discussion. Numerous possibilities have been considered, including genetic and hormonal factors, brain insult and learning. We suggest here that naturally occurring loss of axons of the corpus callosum (either symmetric or asymmetric, with or without neuron death) may be one mechanism underlying the embryological development of hand preference and hemispheric anatomical and functional asymmetries in males. We note supporting evidence for this hypothesis from a report of increased prevalence of left-handedness in children born prematurely at the gestational age prior to the likely onset of axon loss. The practical implications of this hypothesis for clinical management in neonatal intensive care units are discussed. It is suggested that the course of loss of callosal axons may have a genetic component which is associated with a sex-related influence and which is modifiable by prenatal and early postnatal events.

Axons↗

PubMed1991

Effect of prenatal exposure to ethanol on the cell cycle kinetics and growth fraction in the proliferative zones of fetal rat cerebral cortex.

Prenatal exposure to ethanol produces profound changes in the number of neurons in the mature cortex. These changes in neuronal number may reflect ethanol-induced disturbances in early developmental processes, that is in the proliferation of neuronal precursors. Hence, the present study examined the effect of ethanol on cell proliferation in the two neocortical proliferative zones, the ventricular zone (VZ) and subventricular zone (SZ). From gestational day 5 to 21, pregnant rats were fed an ethanol diet (6.7% v/v), pair-fed an isocaloric control diet, or fed chow and water. Pregnant rats were given a series of one to nine injections of bromodeoxyuridine (BrdU). After immunohistochemical processing, the ratio of cells in each proliferative zone that were labeled with BrdU to the total population was determined. The portion of the population that was cycling (growth fraction), the total length of the cell cycle, and the length of the S-phase of the cell cycle were calculated for VZ and SZ cells. Exposure to moderate levels of ethanol has markedly different effects upon the two neocortical proliferative zones. In the VZ, the length of the total cell cycle was significantly greater in ethanol-treated rats than in controls; however, the growth fraction and the length of the S-phase were unaffected by ethanol. In contrast, in the SZ, the growth fraction was significantly greater in ethanol-treated rats, but ethanol had no effect on the length of the total cell cycle or of the S-phase. These differences may underlie the ethanol-induced abnormalities in neuronal generation.

Animals↗

PubMed1990

Heterozygote effects in dreher mice.

The dreher mutation (gene symbol: dr) is an autosomal recessive mutation located on chromosome 1 of the mouse. Homozygous dreher mice (dr/dr) are ataxic, have a white belly spot, a short-tail, inner ear and skeletal malformations, and a variety of CNS abnormalities. Recently in our dreher colony (the drsst-J allele on a B6C3Fe background), we noticed mice with one or more white belly spots typical of drsst-J/drsst-J mice but which were non-ataxic and had a normal tail length; wild-type mice (+/+) of the same genetic background do not have simialr belly spots. Results of three breeding experiments indicate that a new mutation had not occurred, but rather that the spotted, non-ataxic mice are heterozygous dreher mice (drsst-J/+). Histological examination showed that drsst-J/+ mice have abnormalities in the hippocampal formation that are qualitatively similar to those found in drsst-J/drsst-J mice. Most frequently there is an increase in the number of pyramidal cells in CA3 and a marked thickening of the pyramidal cell layer. In contrast to dreher homozygotes the cerebellum appears to have a normal foliation pattern and no discernible laminar abnormalities. Thus, both breeding experiments and histological examination indicate that drsst-J is semidominant. We speculate that drsst-J is a "loss of function" mutation, but, in any event, the presence of phenotypic abnormalities in drsst-J/+ mice may be useful in identifying the primary developmental defect in dreher mice.

Animals↗

PubMed1989

Bromodeoxyuridine immunohistochemical determination of the lengths of the cell cycle and the DNA-synthetic phase for an anatomically defined population.

A cumulative labelling protocol using 5-bromo-2'-deoxyuridine (BUdR) was followed to determine: (1) the growth fraction (i.e., the proportion of cells that comprise the proliferating population), (2) the length of the cell cycle, and (3) the length of the DNA-synthetic phase (S-phase) for proliferative cells in the dentate gyrus of the mouse. On postnatal day 20 (P20), C57BL/6J mice were injected with BUdR at two hour intervals for a total period of 12 hours. Animals were sacrificed at selected intervals, and the brains were processed for immunohistochemistry using a monoclonal antibody directed against single-stranded DNA containing BUdR. The numbers of BUdR-labelled and unlabelled cells in sections through the hilus of the dentate gyrus were counted. The number of BUdR-labelled cells increased linearly from an initial value of about 12% of the total number of cells to a maximum value of just over 24% of the total. These findings indicate that, at P20, a maximum of 24.2 +/- 1.2% of the cells in the dentate hilus are part of the proliferating population. The calculated length of the cell cycle of the cells comprising the intrahilar proliferative zone was estimated to be 16.1 +/- 0.8 h. The length of the S-phase was estimated at 8.0 +/- 0.4 h. In addition, mathematical analysis, using one and two population models, indicates that over 90% of the proliferating cells in the dentate hilus at this age comprise a single population at least in terms of the lengths of the cell cycle and the S-phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Use of bromodeoxyuridine-immunohistochemistry to examine the proliferation, migration and time of origin of cells in the central nervous system.

The use of an exogenously administered thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), for studies of the proliferation, migration and time of origin of cells in the cerebral cortex was investigated and compared with [3H]thymidine [( 3H]dT) autoradiography. Pregnant rats or mice were injected with BrdU and/or [3H]dT and processed by standard immunohistochemical techniques using a primary antibody directed against BrdU in single-stranded DNA, autoradiographic methods, or both. In animals that survived only 1 h after the injection, BrdU-positive cells were distributed in the proliferative zones throughout the central nervous system (CNS). In animals killed 1-3 days after the BrdU injection, intensely immunoreactive cells were in the superficial cortical plate and less intensely labeled cells were scattered throughout the deep cortical plate, the intermediate zone, and the germinal zones. In adult animals, 60 days or more after an injection of BrdU on GD 19, BrdU-positive cells were located in layer II/III of neocortex, the hippocampal pyramidal layer, and the granule layer of the dentate gyrus. In the double-labeling studies, the distribution of BrdU-immunoreactive cells was identical to that of autoradiographically labeled cells, and all autoradiographically labeled neurons were BrdU positive. Thus, BrdU immunohistochemistry is suitable for developmental studies of the CNS; moreover, it provides several advantages over [3H]dT autoradiography.

Animals↗

PubMed1987

Genetic factors and the measurement of exploratory activity.

The progenitor strains C57BL/6 and BALB/c and the seven recombinant inbred strains derived from them were used to examine the genetic relationship between two measures of activity and hippocampal lamination defect (Hld). Fifty-three mice (Mus musculus), 9 from each of the progenitor strains and 5 from each recombinant inbred strain, were tested for 16 min in a device which permitted both unobstructed traverse of the length of a runaway and contact with objects which were aligned alongside the runway. The C57BL/6 mice produced significantly more locomotor (runway traversal) activity, whereas the BALB/c showed significantly greater amounts of investigatory (object contact) activity. This reversal of relative position in the distribution of scores was not present for the recombinant strains. There was no dichotomous separation of recombinant strains for either measure. Examination of activity in terms of four consecutive 4-min periods indicates differences among the strains with respect to changes during the test session. The strains may be dichotomized with respect to decrement in activity within the 16-min session, but these groups do not correspond with those reported by others. The inference of a single genetic determinant for activity measured either as locomotor or investigatory responses is not supported by these data, nor is there any apparent relationship between activity and Hld. The critical influence of genetic-environment interactions in determining behavior and the effect of the selection of measurement techniques upon interpretation of data are emphasized by these data.

Animals↗

PubMed1987

Basic concepts of CNS development.

Some basic principles of the development of the central nervous system (CNS) are reviewed and their implications for both normal and abnormal behavioral development are discussed. The goals of this review are: to provide a set of concepts to aid in the understanding of the variety of complex processes occurring during CNS development, to illustrate how these concepts contribute to our knowledge of the normal anatomy of the adult brain, and to delineate how modifications of normal developmental processes by traumatic injury, by environmental or experiential influences, or by genetic variations may lead to modifications in the resultant structure and function of the adult CNS.

Brain↗

PubMed1985

Dendritic arbors and dendritic excrescences of abnormally positioned neurons in area CA3c of mice carrying the mutation "hippocampal lamination defect".

BALB/cJ and BALB/cByJ mice are homozygous for the autosomal gene "hippocampal lamination defect" (provisional gene symbol: Hld) which produces an abnormality in the lamination of the pyramidal cell layer of area CA3c of the hippocampus such that early-generated neurons are superficial and late-generated neurons are deep. Other inbred strains of mice are wild-type (+/+) at the Hld locus and do not have this inversion in cell position in area CA3c. The Golgi method was used to analyze the dendritic arbors of the abnormally positioned pyramidal cells and to compare the distribution of dendritic excrescences (i.e., the termination sites of the mossy fibers) in +/+ and Hld/Hld mice. It was found that in +/+ mice the late-generated pyramidal cells (whose cell bodies are positioned just below the suprapyramidal mossy fiber layer) have one set of dendritic excrescences on their apical dendrites as they extend through the suprapyramidal mossy fiber layer and a second set on their basal dendrites as they pass through the infrapyramidal mossy fiber layer. In contrast, in Hld/Hld mice the late-generated pyramidal cells (whose cell bodies are abnormally positioned just below the intrapyramidal mossy fiber layer) have two sets of dendritic excrescences on their apical dendrites, as they pass through the intrapyramidal and suprapyramidal mossy fiber layers, and none on their basal dendrites. In addition, in the vicinity of the apparent point of contact of the intrapyramidal mossy fibers, the apical dendrites of some of the abnormally positioned pyramidal cells have several fine-caliber branches.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

The mode of inheritance of a defect in lamination in the hippocampus of BALB/c mice.

In BALB/c mice the lamination of the pyramidal cell layer of area CA3c of the hippocampus is abnormal in that early-generated neurons are superficial and late-generated neurons are deep. To determine the mode of inheritance of this strain difference, the laminar distribution of mossy fibers and hippocampal pyramidal cells was examined using the Timm's sulfide silver method in BALB/c x C57BL/6 F1 and F2 hybrids, in BALB/cByJ and C57BL/6J mice which were fostered to females of the other strain before receiving their first meal, and in the CXB series of recombinant inbred strains (originally derived using BALB/c and C57BL/6 as progenitor strains). The pattern of hippocampal lamination was classified as "BALB/c-like" if pyramidal cells were present below an intrapyramidal mossy fiber layer or as "B6-like" if only an infrapyramidal mossy fiber layer was present. In both male and female CB6F1 and B6CF1 hybrids the distribution of mossy fibers is BALB/c-like. In 7 of 9 F2 hybrids the distribution was BALB/c-like and in the remaining 2 B6-like. In the cross-fostered mice the pattern was always the same as normally raised mice of the same genotype. Of the recombinant inbred strains, 5 (CXBD, CXBG, CXBH, CXBI, and CXBK) had BALB/c-like hippocampal lamination and 2 (CXBE and CXBJ) had B6-like lamination. These results are consistent with inheritance by means of a single autosomal dominant (or semi-dominant) gene. The provisional name "Hippocampal lamination defect" and gene symbol Hld are suggested. The Hld mutation is only the third known neurological mutation in mice which apparently affects neuronal migration, and the fact that it affects only a single subdivision of the hippocampus indicates that Hld may be a useful tool for future studies of the development of the central nervous system and particularly of the cell biology of neuronal migration and neuronal specificity.

Animals↗