Biomedical subjects

R Hawkes

Publications and source records attributed to R Hawkes.

At least 19 recordsLinked to original sources

PubMed2003

The cyclin-dependent kinase 5 activator, p39, is expressed in stripes in the mouse cerebellum.

Cyclin-dependent kinase 5 (Cdk5) activity is required for CNS development. The Cdk5 activator, p35, is well characterized but its isoform, p39, has been less studied. Previously, p39 mRNA expression in rat brain was shown to peak at 3 weeks postnatal, and the level remains high in the adult cerebellum [Neurosci Res 28 (1997) 355]. However, p39 protein expression and specific localization in the cerebellum, where p39 mRNA level significantly exceeds that of p35, have not been examined. Here, we explored the specific cerebellar localization of the p39 protein in the developing and adult mice. Adult cerebellar Purkinje cell somata and dendritic arbors were strongly positive for p39 but only rare and barely detectable p39 was observed in Purkinje cell axons. Cdk5 also localized in Purkinje cell somata and dendrites of the adult cerebellum, but p35 localized only in Purkinje cell somata, further suggesting a functional difference between p35 and p39. During development, cerebellar p39 was first noted at P10. Primary cultures of a developing cerebellum also showed strong p39 immunoreactivity in Purkinje cell somata and dendrites, but weak p39 immunoreactivity in Purkinje cell axons. Starting from P10, p39 was observed in a subset of Purkinje cells that form parasagittal bands throughout the vermis and hemispheres. These bands were bilaterally symmetrical and continuous from one lobule to another. Conversely, Cdk5 and p35 showed a uniform staining pattern. The pattern of p39 closely resembled that of zebrin II/aldolase C, suggesting that p39 may play a role in the adult cerebellum rather than in pattern development. This premise is consistent with the normal pattern of zebrin II/aldolase C zones and stripes in mutant p39-/- mice. The alternating p39 parasagittal band pattern may reflect a role for p39 or Cdk5/p39 in the functional compartmentation of the cerebellum.

Animals↗

PubMed2001

Selective Purkinje cell ectopia in the cerebellum of the weaver mouse.

The adult mouse cerebellar vermis consists of four transverse zones, each of which is further subdivided into parasagittal stripes. In the adult weaver (wv/wv) mouse, the zebrin II expression pattern in the cerebellar vermis is abnormal, consistent with the absence of a central zone (approximately lobules VI/VII). Because the small, heat shock protein HSP25 is a constitutive marker of parasagittal bands of Purkinje cells in the caudal central zone and the nodular zone (approximately lobules IX/X), we used HSP25 immunocytochemistry to show that the patterning abnormalities in wv/wv reflect selective Purkinje cell ectopia rather than the absence of the central zone. A specific HSP25-immunopositive Purkinje cell ectopia within the central zone was identified. Symmetrical clusters of HSP25-immunopositive Purkinje cells, which presumably would have formed the parasagittal stripes in the wild type, are present ectopically on either side of the midline in wv/wv. In contrast, in the nodular zone, HSP25-immunopositive Purkinje cells form a near-monolayer and are organized into parasagittal stripes. We therefore conclude that specific Purkinje cell clusters in the wv/wv cerebellum fail to disperse and that this ectopia contributes to the topographical abnormalities.

Animals↗

PubMed2001

Ectopic expression of tyrosine hydroxylase in Zebrin II immunoreactive Purkinje cells in the cerebellum of the ataxic mutant mouse, pogo.

The pogo mouse is a new ataxic autosomal recessive mutant that arose in an inbred strain (KJR/MsKist) derived from a Korean wild mouse. The phenotype includes difficulty in maintaining normal posture and the inability to walk straight. Several previous studies have associated inherited ataxia with the ectopic expression of tyrosine hydroxylase (TH) in Purkinje cells. Therefore, in the present study, the distribution of TH expression was compared with that of zebrin II in Purkinje cells of adult pogo/pogo mutant mice. In normal control littermates, tyrosine hydroxylase immunoreactivity is confined to a delicate axonal plexus ramifying through the molecular layer. In pogo/pogo, in addition to the axonal plexus, TH-immunoreactive Purkinje cells were present in all lobules of the cerebellar vermis and hemispheres, distributed as series parasagittal bands. The general pattern of expression is reproducible between individuals and symmetrical about the midline. Alternating stripes of TH expression are also seen in the hemispheres, and most Purkinje cells in the paraflocculi and flocculi are immunoreactive. In pogo/+ mice, TH-immunoreactive Purkinje cells are rare. The pattern of zebrin II expression was used to map TH immunoreactive Purkinje cells in pogo/pogo mutant mice. Double immunofluorescence labeling combining anti-zebrin II fand anti-TH showed that all TH-immunoreactive Purkinje cells are zebrin II+, but that many zebrin II+ Purkinje cells within a band do not stain with anti-TH. Taken together with the morphological changes observed in the Purkinje cell axons, this suggests that abnormal Purkinje cell function may contribute to the ataxic phenotype in pogo/pogo mice.

Animals↗

PubMed2001

Aldolase C/zebrin II expression in the neonatal rat forebrain reveals cellular heterogeneity within the subventricular zone and early astrocyte differentiation.

During late gestational and early postnatal development, proliferating cells in the subventricular zones of the lateral ventricles (SVZ) migrate into the gray and white matter of the forebrain and differentiate into astrocytes and oligodendrocytes. Because the cellular composition and structure of the neonatal SVZ is poorly understood, we performed a differential display PCR screen to identify genes preferentially expressed therein. One highly expressed gene encoded aldolase C. We used a specific monoclonal antibody, aldolase C/zebrin II (ALDC/ZII), in combination with markers of glial lineage and proliferation, to characterize the cells that express this gene. In the neonatal SVZ, ALDC/ZII-positive cells, which are generally polygonal and display several processes, have a nonuniform spatial distribution. They do not express vimentin, GFAP, or NG2. A subset of ALDC/ZII-positive cells incorporates bromodeoxyuridine, but progenitors identified by beta-galactosidase expression after infection with recombinant BAG virus do not show ALDC/ZII immunoreactivity. Outside of the SVZ, beta-galactosidase-positive/ALDC/ZII-positive cells have an astrocytic phenotype, suggesting that immunoreactivity was acquired after exit from the SVZ. These studies demonstrate that the neonatal SVZ is composed of different populations of cells that can be characterized by their antigenic phenotype, their proliferative capacity, and their spatial distributions. Nonrandom distributions of different cell types within the SVZ may permit the formation of microenvironments that stimulate the production of cells with specific potentials at appropriate points in development. Analysis of ALDC/ZII expression by astrocyte lineage cells in the neonatal cerebral cortex and white matter may reveal insights into the phenotype and behavior of undifferentiated astrocyte progenitors.

Animals↗

PubMed2001

Abnormal dispersion of a purkinje cell subset in the mouse mutant cerebellar deficient folia (cdf).

Purkinje cells of different molecular phenotypes subdivide the cortex of the cerebellum both rostrocaudally into parasagittal bands and mediolaterally into transverse zones. Superimposed on the Purkinje cell compartmentation, the cerebellar cortex is pleated into a reproducible array of lobes and lobules. During cerebellar development, Purkinje cell bands are formed through the rostrocaudal dispersal of embryonic clusters, triggered primarily by a Reelin-dependent signaling pathway. In the naturally occurring mouse mutant cerebellar deficient folia (cdf), there is a failure of Purkinje cell dispersion that results in widespread Purkinje cell ectopia in the adult. The ectopia is restricted primarily to that subset of Purkinje cells that does not express zebrin II/aldolase C and that forms ectopic clusters in among the cerebellar nuclei. Most Purkinje cells that express zebrin II are located normally in a monolayer. Thus, the cerebellum of cdf mutants has a failure of Purkinje cell dispersion that is confined primarily to a zebrin II-negative (zebrin II(-)) subpopulation. Despite the Purkinje cell ectopia, the parasagittal band organization of the cerebellum is still clear. The shortening of the cortex is distributed evenly over all lobules, with the result that transverse expression boundaries are relocated with respect to the lobules and fissures. The number of Purkinje cells in the cdf/cdf cerebellum is similar to the number in littermate controls. Therefore, it appears that the lesion in cdf results in the failure of a zebrin II(-) Purkinje cell subset to disperse either due to a cell intrinsic defect or due to an abnormal interaction between the Purkinje cells and either granule cells or afferent inputs.

Animals↗

PubMed2001

Constitutive expression of heat shock protein HSP25 in the central nervous system of the developing and adult mouse.

Immunohistochemistry and in situ hybridization have been used to survey constitutive heat shock protein (HSP)25 expression in the brain and spinal cord of the developing and adult mouse. The data reveal both transient and sustained patterns of expression and demonstrate robust differences between mice and rats. During development, HSP25 is transiently expressed in neurons of the inferior colliculus, various thalamic subnuclei, and the majority of Purkinje cells in the cerebellum. Sustained expression into adulthood is seen in neurons of the cranial nerve nuclei, spinal cord motoneurons, median preoptic nucleus, and a subset of Purkinje cells. Differences in HSP25 expression between adult rats and mice include the somatic motor nuclei innervating the extraocular muscles, which are HSP25 immunoreactive only in the rat. Similar differences in HSP25 expression are seen during the development of the inferior colliculus, thalamus, and cerebellum, where expression is restricted to mice.

Animals↗

PubMed2001

NeuroD2 is necessary for development and survival of central nervous system neurons.

NeuroD2 is sufficient to induce cell cycle arrest and neurogenic differentiation in nonneuronal cells. To determine whether this bHLH transcription factor was necessary for normal brain development, we used homologous recombination to replace the neuroD2 coding region with a beta-galactosidase reporter gene. The neuroD2 gene expressed the reporter in a subset of neurons in the central nervous system, including in neurons of the neocortex and hippocampus and cerebellum. NeuroD2(-/-) mice showed normal development until about day P14, when they began exhibiting ataxia and failure to thrive. Brain areas that expressed neuroD2 were smaller than normal and showed higher rates of apoptosis. Cerebella of neuroD2-null mice expressed reduced levels of genes encoding proteins that support cerebellar granule cell survival, including brain-derived neurotrophic factor (BDNF). Decreased levels of BDNF and higher rates of apoptosis in cerebellar granule cells of neuroD2(-/-) mice indicate that neuroD2 is necessary for the survival of specific populations of central nervous system neurons in addition to its known effects on cell cycle regulation and neuronal differentiation.

Animals↗

PubMed2001

Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain.

The dystrophin-associated protein complex (DPC) is required for the maintenance of muscle integrity during the mechanical stresses of contraction and relaxation. In addition to providing a membrane scaffold, members of the DPC such as the alpha-dystrobrevin protein family are thought to play an important role in intracellular signal transduction. To gain additional insights into the function of the DPC, we performed a yeast two-hybrid screen for dystrobrevin-interacting proteins. Here we describe the identification of a dysbindin, a novel dystrobrevin-binding protein. Dysbindin is an evolutionary conserved 40-kDa coiled-coil-containing protein that binds to alpha- and beta-dystrobrevin in muscle and brain. Dystrophin and alpha-dystrobrevin are co-immunoprecipitated with dysbindin, indicating that dysbindin is DPC-associated in muscle. Dysbindin co-localizes with alpha-dystrobrevin at the sarcolemma and is up-regulated in dystrophin-deficient muscle. In the brain, dysbindin is found primarily in axon bundles and especially in certain axon terminals, notably mossy fiber synaptic terminals in the cerebellum and hippocampus. These findings have implications for the molecular pathology of Duchenne muscular dystrophy and may provide an alternative route for anchoring dystrobrevin and the DPC to the muscle membrane.

Amino Acid Sequence↗

PubMed2001

Expression of heat-shock protein Hsp25 in mouse Purkinje cells during development reveals novel features of cerebellar compartmentation.

The small heat shock protein Hsp25 is constitutively expressed in the adult mouse cerebellum by parasagittal stripes of Purkinje cells confined to the caudal central zone ( approximately lobules VI and VII), the nodular zone ( approximately ventral lobule IX and lobule X), and the paraflocculi/flocculi. During development several distinct phases in Hsp25 expression can be distinguished. Hsp25-immunopositive Purkinje cells are first seen at birth, when four clusters are visible in the vermis of lobules IV/V, and scattered Hsp25-immunoreactive Purkinje cells are seen in lobule VIII. By postnatal day 2/3, six narrow parasagittal stripes of Hsp25-immunopositive Purkinje cells are seen in the vermis of the anterior lobe. In the posterior lobules, most Purkinje cells in the vermis of lobules VIII and IX express Hsp25. This initial limited expression is followed by a phase of widespread expression (postnatal days 6-9) in which Hsp25 immunoreactivity is detected in virtually all Purkinje cells. This global cerebellar expression of Hsp25 then gradually disappears, first in the anterior zone and the hemispheres and subsequently in the posterior zone, to leave the restricted adult expression pattern. Western blotting analysis and immunoprecipitation with anti-Hsp25 suggest that all immunocytochemistry can be attributed the expression of Hsp25. Furthermore, visual deprivation had no effect on the development of Hsp25 expression in Purkinje cells, suggesting that visuomotor input is not responsible for the establishment of constitutive Hsp25 expression in the cerebellar cortex.

Age Factors↗

PubMed2001

Patterned cerebellar Purkinje cell death in a transgenic mouse model of Niemann Pick type A/B disease.

Niemann Pick disease is a family of autosomal recessive disorders characterized by cholesterol accumulation. The most common type is Niemann Pick type A/B (NPA/B), resulting from deficient acid sphingomyelinase activity, which leads to sphingomyelin and cholesterol accumulation. The neuropathology of NPA/B includes widespread neuronal degeneration. An acid sphingomyelinase knockout mouse model of NPA/B (ASMKO) has been developed by the targeted deletion of the acid sphingomyelinase gene. When cerebellar morphology was examined in the ASMKO mouse at postnatal day 60 (P60), a dramatic pattern of longitudinal stripes was revealed in which roughly half the Purkinje cells had died, leaving a highly stereotyped, bilaterally symmetrical array of stripes. Antizebrin II immunocytochemistry revealed that the absent Purkinje cells corresponded exactly to the zebrin II-negative subset, leaving the zebrin II-positive subset apparently intact. By P120, some of the zebrin II-positive Purkinje cells had also been eliminated from the posterior vermis and hemispheres. By P180, all Purkinje cells had been lost from the anterior lobe. Finally at P240, almost all Purkinje cells had disappeared to leave a stereotyped distribution in lobules VI, IX-X and the flocculus and paraflocculus. The temporal pattern of Purkinje cell death demonstrates differential susceptibility of morphologically identical cells that appear to be linked to their molecular phenotypes.

Aging↗

PubMed2000

Abnormalities in cerebellar Purkinje cells in the novel ataxic mutant mouse, pogo.

The pogo mouse is a novel neurological mutant, which was discovered, in an inbred strain (KJR/MsKist) derived from a Korean wild mouse. The pathological manifestations include difficulty in maintaining normal posture, failures of interlimb coordination and the inability to walk straight. The ataxia is first apparent from about 2 weeks of age and progresses throughout life. The mutation is inherited as an autosomal recessive trait. In this report, we describe abnormalities in the pogo/pogo cerebellum. Nissl staining shows that the pogo/pogo cerebellum is normal in size and lobulation. Similarly, immunocytochemical staining for a granule cell marker, 10B5, shows no differences in the thickness of the granular layer between pogo/pogo homozygote and pogo/+ heterozygote littermate controls. By using anti-parvalbumin immunocytochemistry, the cells of molecular layer of the pogo/pogo cerebellum also appeared similar in distribution as compared to normal wild type mouse. In anti-neurofilament immunocytochemistry, the basket cells axons of the pogo/pogo cerebellum appeared normal. Purkinje cell abnormalities were identified by using anti-calbindin D immunocytochemistry. In 120-day-old pogo/pogo mutant mice there was a loss of Purkinje cells throughout the cerebellar vermis. Furthermore, the somata and dendrites were extensively vacuolated in the pogo/pogo Purkinje cells and the primary dendrites were frequently swollen. Focal axonal swellings were commonly observed in the Purkinje cell axons of pogo/pogo mutant mice as they traversed the granular layer. These data suggest that the progressive ataxia seen in pogo mice may be due to a failure of normal Purkinje cell activity.

Animals↗

PubMed2000

Constitutive expression of the 25-kDa heat shock protein Hsp25 reveals novel parasagittal bands of purkinje cells in the adult mouse cerebellar cortex.

Despite the reported absence of the 25-kDa heat shock protein Hsp25 in the rodent cerebellum, we have determined that Hsp25 is constitutively expressed in a subset of Purkinje cells in the adult cerebellum of the mouse. No other cerebellar neurons are Hsp25 immunoreactive, but there is weak staining associated with blood vessels. In the vermis, Hsp25-immunoreactive Purkinje cells are confined to two regions: one in lobules VI/VII, the other in lobules IX/X. In each region, only a subset of the Purkinje cells is immunoreactive. These cells are grouped in five parasagittal bands arranged symmetrically about the midline. The boundaries of these expression domains correspond to transverse zones previously inferred from other expression patterns. A third Hsp25-immunopositive domain is seen in the paraflocculus and flocculus. Again, only a subset of Purkinje cells within the paraflocculus and flocculus express Hsp25, revealing three distinct bands. Previous descriptions of compartmentation antigens have not differentiated between adult populations of Purkinje cells in these regions, suggesting that Hsp25 is a novel compartmentation antigen in the adult cerebellum.

Animals↗

PubMed2000

A serological re-evaluation of acute non-A non-B hepatitis from the early 1970s.

BACKGROUND: The epidemiology and natural history of recently discovered viruses, which may be responsible for cases of seronegative infectious hepatitis, are currently being investigated. Retrospective studies of stored sera can provide a historical perspective of these infections. AIMS: To re-evaluate the serological, demographic and clinical characteristics of patients hospitalised in the early 1970s with acute hepatitis. METHODS: The stored sera of 57 patients hospitalised between 1971 and 1974 with acute hepatitis, designated at that time as non-A non-B (NANB) hepatitis, were re-tested using commercially available enzyme-linked immunosorbent assays (ELISAs) for the presence of anti-hepatitis A virus (HAV) IgM, hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) IgG, and anti-hepatitis E virus (HEV) IgG. Stored sera from a group of 57 patients concurrently hospitalised for other conditions were also tested. Detailed records of the original epidemiological interviews were examined to compare patient demographics, risk factors for infectious hepatitis and clinical data for the NANB hepatitis group and an original control group of 604 hospitalised patients. RESULTS: Serum from 15 of the 57 (26%) previously designated NANB hepatitis cases had elevated anti-HAV IgM and are likely to represent missed cases of hepatitis A. Thirteen (23%) of cases previously designated as NANB hepatitis had positive hepatitis C antibody tests. These patients were younger and significantly more likely to have used intravenous drugs than control patients. Three NANB hepatitis and two hospital control patients were anti-HEV IgG antibody positive. All of these individuals were born in, or had travelled to, developing countries. Serum from 27 (47%) of the NANB hepatitis patients were negative on all tests. These hepatitis non-A-E cases included children and elderly adults, but as a group were significantly more likely to have used intravenous drugs than hospitalised control patients. CONCLUSION: Both HCV and probable non-A-E virus(es) were important causes of acute NANB hepatitis during the early 1970s.

Adolescent↗

PubMed2000

Pattern formation in the cerebellar cortex.

The cerebellar cortex is subdivided rostrocaudally and mediolaterally into a reproducible array of zones and stripes. This makes the cerebellum a valuable model for studying pattern formation in the vertebrate central nervous system. The structure of the adult mouse cerebellar cortex and the series of embryological events that generate the topography are reviewed.

Adult↗

PubMed1999

Different dystrophin-like complexes are expressed in neurons and glia.

Duchenne muscular dystrophy is a fatal muscle disease that is often associated with cognitive impairment. Accordingly, dystrophin is found at the muscle sarcolemma and at postsynaptic sites in neurons. In muscle, dystrophin forms part of a membrane-spanning complex, the dystrophin-associated protein complex (DPC). Whereas the composition of the DPC in muscle is well documented, the existence of a similar complex in brain remains largely unknown. To determine the composition of DPC-like complexes in brain, we have examined the molecular associations and distribution of the dystrobrevins, a widely expressed family of dystrophin-associated proteins, some of which are components of the muscle DPC. beta-Dystrobrevin is found in neurons and is highly enriched in postsynaptic densities (PSDs). Furthermore, beta-dystrobrevin forms a specific complex with dystrophin and syntrophin. By contrast, alpha-dystrobrevin-1 is found in perivascular astrocytes and Bergmann glia, and is not PSD-enriched. alpha-Dystrobrevin-1 is associated with Dp71, utrophin, and syntrophin. In the brains of mice that lack dystrophin and Dp71, the dystrobrevin-syntrophin complexes are still formed, whereas in dystrophin-deficient muscle, the assembly of the DPC is disrupted. Thus, despite the similarity in primary sequence, alpha- and beta-dystrobrevin are differentially distributed in the brain where they form separate DPC-like complexes.

Amino Acid Sequence↗

PubMed1999

Transverse zones in the vermis of the mouse cerebellum.

The mouse cerebellar cortex is subdivided by an elaborate array of parasagittal and transverse boundaries. The relationship between these two orthogonal patterns of compartmentation is understood poorly. We have combined the use of adult and perinatal molecular markers of compartmentation-zebrin II, calbindin, and an L7/pcp-2-lacZ transgene-to resolve some of these issues. Our results indicate that the adult cerebellar vermis is divided along the rostrocaudal axis by three transverse boundaries: through the rostral face of lobule VI, in the caudal half of lobule VII, and across the posterolateral fissure between lobules IX and X. These three boundaries subdivide the vermis into four transverse zones: the anterior zone (lobules I-V), the central zone (lobules VI-VII), the posterior zone (lobules VIII-IX), and the nodular zone (lobule X). The same zones and boundaries also can be identified in the newborn cerebellum. The parasagittal organization is different in each zone: a unique combination of Purkinje cell phenotypes is found in each transverse zone both in the neonate and the adult, and different zones have distinct developmental time tables. Furthermore, the parasagittal bands of Purkinje cells revealed in the adult cerebellar cortex by using antizebrin II immunocytochemistry are discontinuous across the transverse boundaries. These data suggest that the transverse zones of the vermis form first during development and that parasagittal compartmentation develops independently in each transverse zone.

Animals↗

PubMed1999

Spatial correspondence between tactile projection patterns and the distribution of the antigenic Purkinje cell markers anti-zebrin I and anti-zebrin II in the cerebellar folium crus IIA of the rat.

We have compared the band-like distribution of the Purkinje cell-specific polypeptides zebrin I and zebrin II with the spatial organization of tactile projections to crus IIa in the cerebellar hemisphere of the rat. Maps of tactile responses in the granular layer of the cerebellar hemispheres are fractured into discontinuous regions, termed "patches". High-density micromapping was used to identify specific patches and their boundaries within this fractured somatotopic map. In one series of experiments, medial and lateral boundaries of the large central ipsilateral upper lip-related patch were identified and labeled with either Fast Blue or India Ink. Following immunocytochemical processing, the band-like distribution of immunostained Purkinje cells (zebrin-positive bands) and the identified patch boundaries were digitized and reconstructed in three dimensions. Comparisons between these two features demonstrate a spatial correspondence between zebrin transitions and the boundaries of the electrophysiologically defined upper lip-related patch. In another series of experiments, we outlined the boundaries or centers of several smaller patches consistently located in the medial portion of the folium. Again, we found a correspondence between the distribution of granule cell layer tactile patches and the zebrin staining pattern. The correspondence between tactile projection patterns and molecular features demonstrated in the present study implies that there is a distinct and largely fixed spatial pattern of organization in the cerebellar hemispheres. We discuss possible causal connections and developmental determinates, as well as the physiological significance of the correspondence between the two features.

Afferent Pathways↗

PubMed1999

Granule cell dispersion is restricted across transverse boundaries in mouse chimeras.

The granular layer of the developing and adult cerebellum is marked by the presence of several transverse boundaries, revealed in gene expression patterns or as a consequence of genetic mutations. It is unclear whether these boundaries represent fundamental differences between granule cell populations or if they are a secondary response to regional differences in the underlying Purkinje cells. One possibility is that boundaries mark different spatial domains of granule cells in a lineage-dependent fashion. To test this hypothesis, we have analysed a series of murine embryonic stem cell chimeras marked by the constitutive expression of beta-galactosidase in donor granule cells. The chimeras show a consistent spatial restriction boundary, located in the granular layer of lobule VI in the vermis and extending laterally into crus I of the hemispheres. A second boundary was found separating lobules IX and X in the vermis. No correlation was found between the genotypes of molecular layer interneurons and the underlying granule cells, suggesting that they arise independently. No transverse boundaries were observed for the molecular layer interneurons, consistent with the hypothesis that they are not generated from precursors in the external granular layer. These results indicate that the granular layer of the cerebellum comprises cellular domains with different histories separated by consistent spatial restriction boundaries.

Animals↗