Showing papers on "Radial glial cell published in 1997"

Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex

Abstract: During neuronal migration to the developing cerebral cortex, neurons regulate radial glial cell function and radial glial cells, in turn, support neuronal cell migration and differentiation. To study how migrating neurons and radial glial cells influence each others' function in the developing cerebral cortex, we examined the role of glial growth factor (a soluble form of neuregulin), in neuron-radial glial interactions. Here, we show that GGF is expressed by migrating cortical neurons and promotes their migration along radial glial fibers. Concurrently, GGF also promotes the maintenance and elongation of radial glial cells, which are essential for guiding neuronal migration to the cortex. In the absence of GGF signaling via erbB2 receptors, radial glial development is abnormal. Furthermore, GGF's regulation of radial glial development is mediated in part by brain lipid-binding protein (BLBP), a neuronally induced, radial glial molecule, previously shown to be essential for the establishment and maintenance of radial glial fiber system. The ability of GGF to influence both neuronal migration and radial glial development in a mutually dependent manner suggests that it functions as a mediator of interactions between migrating neurons and radial glial cells in the developing cerebral cortex.

Reelin mRNA Expression During Mouse Brain Development

Abstract: Using in situ hybridization, expression of the mRNA for reelin, the gene most probably responsible for the reeler trait, was studied during mouse brain development, from embryonic day 13 to maturity. The highest level of expression was found in Cajal-Retzius neurons, while a high signal was also seen in the olfactory bulb, the external granular layer of the cerebellum and, particularly at early developmental stages, in hypothalamic differentiation fields, tectum and spinal cord. A moderate to low level of expression was found in the septal area, striatal fields, habenular nuclei, some thalamic nuclei, particularly the lateral geniculate, the retina and some nuclei of the reticular formation in the central field of the medulla. Paradoxically, no reelin expression was detected in radial glial cells, the cortical plate, Purkinje cells, inferior olivary neurons and many other areas that are characteristically abnormal in reeler mutant mice. Together with other preliminary studies, the present observations suggest that the action of reelin is indirect, possibly mediated by the extracellular matrix. Most of the data can be explained by supposing that reelin is a cell-repulsive molecule which prevents migrating neurons from invading reelin-rich areas, and thus facilitates the deployment of radial glial cell processes and the formation of early architectonic patterns.

Early effects of iodine deficiency on radial glial cells of the hippocampus of the rat fetus. A model of neurological cretinism.

Abstract: The most severe brain damage associated with thyroid dysfunction during development is observed in neurological cretins from areas with marked iodine deficiency. The damage is irreversible by birth and related to maternal hypothyroxinemia before mid gestation. However, direct evidence of this etiopathogenic mechanism is lacking. Rats were fed diets with a very low iodine content (LID), or LID supplemented with KI. Other rats were fed the breeding diet with a normal iodine content plus a goitrogen, methimazole (MMI). The concentrations of -thyroxine (T4) and 3,5,3'triiodo--thyronine (T3) were determined in the brain of 21-d-old fetuses. The proportion of radial glial cell fibers expressing nestin and glial fibrillary acidic protein was determined in the CA1 region of the hippocampus. T4 and T3 were decreased in the brain of the LID and MMI fetuses, as compared to their respective controls. The number of immature glial cell fibers, expressing nestin, was not affected, but the proportion of mature glial cell fibers, expressing glial fibrillary acidic protein, was significantly decreased by both LID and MMI treatment of the dams. These results show impaired maturation of cells involved in neuronal migration in the hippocampus, a region known to be affected in cretinism, at a stage of development equivalent to mid gestation in humans. The impairment is related to fetal cerebral thyroid hormone deficiency during a period of development when maternal thyroxinemia is believed to play an important role.

Radial glial cell development and transformation are disturbed in reeler forebrain.

Abstract: Radial glia are among the earliest cell types to differentiate in the developing mammalian forebrain. Glial fibers span the early cortical wall, forming a dense scaffold; this persists throughout corticogenesis, providing a cellular substrate which supports and directs the migration of young neurons. Although the mechanisms regulating radial glial cell development are poorly understood, a secreted cortical radial glial differentiation signal was recently identified in the embryonic mouse forebrain. This signal is abundant at the time radial glia function to support neuronal migration, and down-regulated perinatally, when radial glia are known to undergo transformation into astrocytes. Therefore, it seems that this signal functions as a radial glial maintenance factor, the availability of which regulates the phenotype of cortical astroglia. Here the differentiation signal is further characterized as RF60, a protein with a molecular weight of approximately 60 kD. In addition, the neurologic mutant mouse reeler provides a genetic model for analysis of RF60 function. Radial glia in reeler cortex are shown to be poorly differentiated and the radial scaffold is shown to be maintained for a shorter time than normal. Furthermore, although astroglial cells from normal cortex are induced to elaborate a radial phenotype by RF60, reeler astroglia show an impaired differentiation response to this. These findings suggest that an intrinsic defect in glial differentiation contributes to the phenotype of abnormal cortical lamination seen in reeler mouse, and indicate that RF60 may play a critical role in normal cortical patterning. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 459–472, 1997

Environmental and genetic determinants of neural migration and postmigratory survival.

Abstract: The study of genetic/epigenetic/environmental factors underlies all therapeutic and preventive approaches in fetal, perinatal and paediatric neurology, including rehabilitation. In this paper, we selected a few targets of environmental determinants of brain development leading to underlying priorities for protection of the developing brain. Preparation of the neural germinative epithelium has to be protected against noxious pharmacological agents. New tools have been developed to improve early neural teratology, including the whole-embryo culture method. The neopallial astrocytic precursors have a dual origin. Astrocytes of the white matter and deep neocortical layers derive from transformed radial glial cells, whereas astrocytes of the upper neocortical layers derive from astrocytic precursors that migrate from the late germinative zone after the end of neuronal migration. Among numerous factors able to interfere with these gliogenetic events are the control factors of the lysosomal and autophagic functions, interfering with radial glial cell transformation into astrocytes. All lesions interrupting the migratory corridors of late astroglial migration can produce cytoarchitectonic disturbances of the neocortical supragranular layers, with long-term consequences. The developing brain is weltering in a complex mixture including newly recognized excitotoxic substances, cytokines and growth factors. These substances are sometimes environmental friends like maternal vasointestinal peptide, which prevents brain intrauterine growth retardation. They are sometimes excellent endogenous friends like neurotrophic excitatory agents in physiological conditions. They become often dangerous killers triggered by environmental signals like hypoxias/ischaemias and toxins produced by intrauterine infections, launching the excitotoxic cascade. In this paper, we reviewed mainly environmental determinants interfering with neural cytogenesis and histogenesis during the embryonic, fetal and neonatal span of early life.

Developmental expression, pattern of distribution, and effect on cell aggregation implicate a neuron-glial junctional domain protein in neuronal migration

Abstract: We developed a panel of monoclonal antibodies to cerebellar astroglial cells and selected for study those that revealed microdomain structures on the cell surface of neocortical and cerebellar astrocytes. One antibody, 15D7-AD7, recognized the approximately 72 kDa polypeptide doublet that was identified previously by the polyclonal antibody D4 as a component of the microdomain structure formed between migrating neurons and radial glial cell processes (Cameron and Rakic [1994] J. Neurosci. 14:3139-3155). Immunofluorescent localization studies reveal a spatial and temporal pattern of 15D7 immunoreactivity in multiple brain regions that correlates well with time periods when neuronal cell migration is a prominent morphogenetic event. In areas where the process of migration is underway, 15D7 immunoreactivity is detected simultaneously in both radial glial cells and cells that have the positional and morphologic features characteristic of migrating neurons. Subsequent to the completion of migration, immunoreactivity is detected in the transitional forms of radial glial cells and mature astrocytes, but not in neurons. Cell aggregation analyses reveal that 15D7 antibodies perturb the rate of aggregation for astrocyte-astrocyte, neuron-neuron, and mixed cell-cell combinations. Taken together, the present studies suggest that the polypeptides recognized by the 15D7 antibodies likely participate in an adhesive process, principally within the ventricular and subventricular zones, that is essential at the onset of the cell migration process.

Overexpression of nestin and vimentin in the ependyma of spinal cords from hydrocephalic infants.

Abstract: The ependyma of the spinal central canal in cases of hydrocephalus shows abnormalities which vary with the aetiology of ventricular dilatation. To determine whether these ependymal changes are developmental or reactive in nature, immunohistochemical findings were compared between nine normal controls and 12 cases of hydrocephalus (three each of congenital aqueductal stenosis, Dandy-Walker malformation, Chiari type II malformation, and post-haemorrhagic hydrocephalus) using antisera to nestin, vimentin and glial fibrillary acidic protein. The main pathological findings were disruption of ependymal layer, apparent pseudostratification of ependyma, expansion, cleft or syrinx formation in relation to the central canal, and ependymal rosette formation. In normal developing fetal spinal cord, nestin and vimentin were expressed mainly in pseudostratified ependymal cells and radial fibres in the median septum. In cases with congenital hydrocephalus (congenital aqueductal stenosis, Dandy-Walker malformation, and Chiari type II malformation), nestin was overexpressed in immature ependymal cells, and strong vimentin immunoreactivity was detected in the long tract of radial fibres in the median septum. Nestin and vimentin were also expressed in small cells and their fibres which covered areas denuded of ependymal cells in cases of Chiari type II malformation and post-haemorrhagic hydrocephalus. Two conclusions are suggested by this report. First, the ependyma of the spinal central canal in congenital hydrocephalus shows a delay in maturation of radial glial cells into mature astrocytes and ependymal cells. Second, areas of ependymal denudation may be repaired by the immature glial cells derived from subependymal cells.

Finding a Role for Cajal-Retzius Cells in Cerebral Cortex Development

Abstract: Despite the important advances in unravelling the developmental history of the mammalian neocortex (Rakic 1977; O’Leary 1989), many unanswered questions still remain. Among these questions, one has been puzzling neuroscientists for over a century: what is the function of a distinct population of neurons known as the Cajal-Retzius cells (CR-cells)? These neurons, the first cortical cells to proliferate and differentiate, were reported by Cajal (1890) in the cortex of neonatal rodents and by Retzius (1891) in the developing human neocortex. CR-cells, together with subplate neurons (Allendoerfer and Shatz 1994), form the primordial plexiform layer or preplate. The subsequent appearance of the cortical plate, within the preplate, subdivides the latter into an outer and inner zone, which contain, respectively, mainly the CR-cells and the subplate neurons (Marin- Padilla 1971). Both categories of neurons have a transient life, and the majority undergo a process of cell death at the end of the neocortical ontogeny. Investigations carried out in the 1980s succeeded in demonstrating that subplate neurons have the important role of orienting extracortical afferent projections, particularly thalamocortical fibers, toward their still proliferating cortical target areas (Shatz et al. 1988; Ghosh et al. 1990; Allendoerfer and Shatz 1994). Subplate neu-rons are, therefore, essential for the formation and reshaping of thalamocortical afferents.

Genetic and Environmental Determinants of Neocortical Development: Clinical Applications

Abstract: This chapter reviews the conceptual and methodological tools that permit us to analyze the influences of genetic, epigenetic and environmental determinants on developing neural tissue, including developing neocortex, during early life During the period of preparation of the neural germinative epithelium, environmental influences, including nutritional, circulatory, maternal and placental factors, can interfere with the genetic program in a very complex way Whole postimplantation mouse embryo cultures are a powerful tool for the study of environmental, nutritional, hypoxic and genetic factors at this developmental phase At this step we review particularly the role of recently recognized growth and neurotrophic factors [such as vasointestinal peptide (VIP)] on brain growth, an avenue to explore microcephaly and intrauterine growth retardation At the step of neuronal migration, we review mainly the alcohol and cocaine-induced disturbances of corticogenesis Alcohol and cocaine interfere with the development of the human fetal brain The teratogenic mechanisms of these drugs on neurogenesis were recently explored in animal models Cocaine severely disturbs neocortical architecture, disrupting horizontal and vertical lamination and inducing an abnormal array of the axonal-dendritic bundles Cocaine also alters several steps of gliogenesis The severity of malformations is variable but is evident in all animals exposed to doses comparable to the doses by human cocaine abusers The cocaine-induced cortical pattern seems to be the result of dyschronologic mitoses and of a defect of the radial glial cells This pattern may represent the pathological basis of the neuropsychological modifications described in in utero cocaine-exposed children Immediate early genes (IEGs; c-fos, c-jun, and zif-268) are disturbed by cocaine during development As transcription factors IEGs can directly dysregulate target genes Ethanol locally enhances cell death in the primitive neuroepithelium During neuronal migration, ethanol induces a premature transformation of the radial glial guides into astrocytes Ethanol also inhibits late gliogenesis The resulting postmigratory neocortex displays an abnormal neuronal pattern almost completely deprived of vertical columnization These glial-neuronal disturbances can explain neuropathological and clinical features of the fetal alcohol syndrome At the end of and after neuronal migration, the infragranular layers are a sensitive target for perfusion failures/ hypoxias around mid-gestation During the second half of pregnancy, the transformation of radial glial cells into astrocytic precursors is a target for environtmental disturbances, among which nutritional factors and hypoxial/ischemia are candidates Several residual neuronal migrations or displacements occurring after mid-gestation have complex pathophysiological relationships with ischemia/hypoxia and with circulatory events The late germinative zone produces migrating astrocytic precursorsfor the upper neocortex If confirms the dual origin of astocytic precursors and suggest the transitory existence of a late astroglial pro-tomap destined to upper cortex, which could explain cortical consequences of periventricular leucomalacias (PVLs) and intraventricular hemorrhages (IVHs)