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PubMed1978

Quantitative characteristics of the Feyrter cells and neuroepithelial bodies of the fetal rabbit lung in normoxia and short term chronic hypoxia.

We report here quantitative data on the Feyrter (single) cells (APUD cells) and neuroepithelial bodies (grouped Feyrter cells), in the lungs of rabbit fetuses at 26, 27.5 and 29 days gestational age, during normoxia and short term chronic hypoxia. The apparent number of these cells declines during this period; we suggest that this might be due to increased hypoxemia. Moreover, the number of cells in the lungs of fetuses from short term chronically hypoxic mothers is lower than in the normoxic animals. These findings are in agreement with our previous studies in short term chronically hypoxic neonatal rabbits, and suggest that the increased hypoxemia in the fetus, caused by the induction of hypoxia in the mother, constitutes a stimulus for secretory activity of the Feyrter cells and neuroepithelial bodies (NEBs). This in turn could be part of the mechanism responsible for maintaining the pulmonary vasoconstriction due to hypoxemia. Our results from fetuses of normoxic does provide base line data on the chronological importance of the Feyrter cells and NEBs.

APUD Cells↗
PubMed1992

Evidence for the coexistence of serotonin and calcitonin gene-related peptide at the subcellular level in neuroepithelial bodies in the lung of a marsupial, Isoodon macrourus.

The coexistence of serotonin and calcitonin gene-related peptide (CGRP) in neuroepithelial bodies of the bandicoot, Isoodon macrourus, has been examined using immunocytochemistry at the light- and electron-microscope levels. The avidin-biotin technique of antigen localisation was used initially to identify serotonin-like and CGRP-like immunoreactivity (-LI). Serotonin-LI and CGRP-LI were found in neuroepithelial cells in the lungs of 30-day-old bandicoots. CGRP-LI could also be demonstrated in nerve fibres associated with some neuroepithelial bodies. The protein A-gold technique of antigen localisation was used to label neuroepithelial cells and nerve fibres at the subcellular level. Serotonin-LI and CGRP-LI were observed in the same dense-cored vesicles of most neuroepithelial cells; however, some neuroepithelial cells were shown to possess serotonin-LI without CGRP-LI. Nerve fibres immediately adjacent to neuroepithelial bodies exhibited mainly CGRP-LI. These results show that serotonin-LI and CGRP-LI are present in neuroepithelial cells of the bandicoot in the same secretory vesicles. This pattern of co-localisation may reflect co-ordinated or synergistic actions of these two neuroactive substances.

Animals↗
PubMed1984

Fine structural aspects of the cranial neuroepithelium in early embryos of the rhesus monkey.

Temporal changes in the ultrastructure of cranial neuroepithelial cells and their developmental interactions with adjacent chordamesodermal cells were analyzed during early neurogenesis in rhesus monkey embryos at stages 8-12 (19-28 days of gestation). In the neural plate and early neural fold stages, microtubules and apical microfilaments are not as prominent in the neuroepithelial cells as they are after the neural tube closes, whereas gap junctional vesicles are more evident prior to closure. Initially, the association between neuroepithelial cells and the presumptive notochordal cells is relatively closer than that between neuroepithelial cells and mesenchymal cells. After neural tube closure, the notochord becomes more distant. Cytoplasmic processes from neuroepithelial cells, notochordal cells, and mesenchymal cells interact via the neural basal lamina. In the rhesus monkey embryo, the ultrastructural features of neuroepithelial cells and their interactions with adjacent chordamesodermal cells are similar to those which have been observed in the mouse at comparable stages of gestation.

Animals↗
PubMed2006

[Pre-administration of Ganoderma lucidum spore reduces incidence of neural tube defects induced by retinoic acid in pregnant mice].

OBJECTIVE: To explore whether pre-administration of Ganoderma lucidum spore (GASP) can reduce incidence of neural tube defects (NTDs) induced by all-trans retinoic acid (ATRA) in pregnant mice. METHODS: Twenty pregnant mice were randomly divided into four groups: normal control group, solvent-treated group, ATRA-induced group, and GASP-treated plus ATRA-induced group. GASP solution, which was prepared with solvent (sodium carboxymethyl cellulose), was fed to the pregnant mice in the GASP-treated plus ATRA-induced group twice a day from embryo (E) 0 d to E10.5 d. The same dose of solvent was given to the pregnant mice in the solvent-treated group. At E7.75 d, ATRA (50 mg/kg) was given to the pregnant mice in both ATRA-induced group and GASP-treated plus ATRA-induced group for single time. Embryos were sampled from pregnant mice at E10.5 d. Then the incidence rate of NTDs in mouse embryo was calculated and the crown-rump length of mouse embryo was measured. The positive rate of nestin expression and the distribution of cell cycle of embryonic neural tube neuroepithelial cells were detected by histochemical staining technique and flow cytometry respectively. Reverse transcription-polymerase chain reaction method was used to detect the gene expressions of cyclin-dependent protein kinase 2 (Cdk2) and Cdk4 mRNAs. RESULTS: The incidence rates of NTDs in mouse embryos in the ATRA-induced group and the GASP-treated plus ATRA-induced group were 79.41% and 21.67% respectively, while the crown-rump length of mouse embryos in these two groups were (3.62+/-1.27) mm and (5.84+/-0.92) mm respectively. The positive rate of nestin expression in embryonic neural tube neuroepithelial cells of mouse embryo at E10.5 d in the ATRA-induced group was 32.44%, while that in the GASP-treated plus ATRA-induced group was 77.65%. The cell cycle of embryonic neural tube neuroepithelial cells was obviously arrested at G(0)/G(1) phase in the ATRA-induced group as compared with that in the GASP-treated plus ATRA-induced group. The Cdk4 mRNA was transcripted at a high level in embryonic neural tube in the GASP-treated plus ATRA-induced group, but the Cdk2 mRNA was not detected in this group. CONCLUSION: Pre-administration of GASP can reduce the incidence of NTDs induced by ATRA in pregnant mice.

Animals↗
PubMed2006

Methyl-CpG binding proteins are involved in restricting differentiation plasticity in neurons.

Neurons and astrocytes are generated from common neural precursors, yet neurogenesis precedes astrocytogenesis, which normally commences at later stages of development. We have previously reported that a particular cytosine residue within a STAT3-binding site in the astrocyte-specific marker glial fibrillary acidic protein (GFAP) gene promoter becomes demethylated in neuroepithelial cells as gestation proceeds. This demethylation correlates tightly with the onset of astrocyte differentiation, suggesting that a change in DNA methylation at cell-type-specific gene promoters controls the switch from neurogenesis to astrocytogenesis in the developing brain. Here, we show that late-gestation neuroepithelial cells, which have already lost the methylation in the STAT3-binding site within the GFAP promoter, can still give rise to neurons and that these neurons do not respond to a STAT3-activating cytokine to express GFAP. Members of a transcriptional repressor family, the methylated-CpG binding proteins (MBDs), including MeCP2, are predominantly expressed in neurons, and ectopic MeCP2 expression inhibited astrocyte differentiation of neuroepithelial cells. Moreover, we found that exon 1 of the GFAP gene remains hypermethylated even in neuroepithelial cells at a late developmental stage and in neurons differentiated from such neuroepithelial cells. We further demonstrate that MeCP2 actually binds to the highly methylated exon 1 of the GFAP gene in neurons. These results suggest that region-specific DNA methylation and MBDs play an important role in the regulation of differentiation plasticity in neurons.

Animals↗
PubMed1980

Adenovirus type 12-induced rat tumor cells of neuroepithelial origin: persistence and expression of the viral genome.

Four cell lines derived from adenovirus type 12-induced rat brain tumors were studied. The polyploid cells displayed neuroepithelial characteristics and were transplantable into syngeneic rats and nude mice. In tissue culture the cells grew in monolayers and multilayers. A very high saturation density was reached, and the cells plated in agar and were easily agglutinated with low concentrations of concanavalin A. Between 2 and 11 copies of the viral genome per diploid cellular genome were detected by reassociation kinetics analysis in the different lines. The patterns of distribution of viral DNA sequences in these lines, as revealed by blot analysis, suggest colinear integration of the intact viral genome into the cellular DNA. The patterns of integration were stable after more than 15 months of prolonged tissue culture and after animal reimplantation. Integration patterns were identical in three of the tumor lines and different in another line. Viral sequences were transcribed. The extent of homology found toward adenovirus type 12 DNA in polyadenylated polysome-associated mRNA isolated from the tumor lines suggests that the early and some of the late genes of adenovirus type 12 DNA are transcribed in these tumor cells. Infectious virus was not rescuable from these lines.

Adenoviruses, Human↗
PubMed1988

Fine structure of the fungiform papilla in a ranid frog (Rana esculenta).

The freetop of the fungiform papilla shows a sensorial area about 100 micron in diameter, surrounded by a ring of ciliated cells. Externally to the ciliated cells, i.e., in the lateral wall, numerous large goblet cells can be seen devoid of their mucous content. The sensorial area is composed by three types of cells: mucous, supporting, and neuroepithelial cells. Mucous cells form the most superficial layer, while the cell bodies of the other two are deep, and from them basal and apical processes arise. The above mentioned cells are connected by desmosomes preferentially located between the mucous and the supporting cells, rather than between the supporting and the neuroepithelial cells. The lateral wall of the papilla is made up of a multilayered epithelium that comprises two types of cells: the first type contains electron-dense granules and an abundant rough endoplasmic reticulum, the others are ciliated cells. In the connective axis of the papilla, numerous fenestrated capillaries with endothelial vesiculated cells and nerve fibers are found.

Animals↗
PubMed2007

Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe.

BACKGROUND: The choice of a stem cell to divide symmetrically or asymmetrically has profound consequences for development and disease. Unregulated symmetric division promotes tumor formation, whereas inappropriate asymmetric division affects organ morphogenesis. Despite its importance, little is known about how spindle positioning is regulated. In some tissues cell fate appears to dictate the type of cell division, whereas in other tissues it is thought that stochastic variation in spindle position dictates subsequent sibling cell fate. RESULTS: Here we investigate the relationship between neural progenitor identity and spindle positioning in the Drosophila optic lobe. We use molecular markers and live imaging to show that there are two populations of progenitors in the optic lobe: symmetrically dividing neuroepithelial cells and asymmetrically dividing neuroblasts. We use genetically marked single cell clones to show that neuroepithelial cells give rise to neuroblasts. To determine if a change in spindle orientation can trigger a neuroepithelial to neuroblast transition, we force neuroepithelial cells to divide along their apical/basal axis by misexpressing Inscuteable. We find that this does not induce neuroblasts, nor does it promote premature neuronal differentiation. CONCLUSION: We show that symmetrically dividing neuroepithelial cells give rise to asymmetrically dividing neuroblasts in the optic lobe, and that regulation of spindle orientation and division symmetry is a consequence of cell type specification, rather than a mechanism for generating cell type diversity.

Animals↗
PubMed2001

Asymmetric segregation of Numb in retinal development and the influence of the pigmented epithelium.

Asymmetric segregation of cell-fate determinants during cytokinesis plays an important part in controlling cell-fate choice in invertebrates. During Drosophila neurogenesis, for example, asymmetric segregation of the Numb protein, which inhibits Notch signaling, is necessary for the two daughter cells of a division to have different fates. In vertebrates, the role of asymmetric segregation of cell-fate determinants is uncertain, and the way the process might be regulated is unknown. We have studied the orientation of cell divisions and the distribution of Numb in the developing rat retina. We show that, whereas most retinal neuroepithelial cells divide with their mitotic spindles oriented parallel to the plane of the neuroepithelium, a substantial minority divides with their spindles oriented perpendicularly. The proportion of these vertically dividing cells changes during development, peaking around the day of birth. Numb appears to be inherited only by the apical daughter cell when a neuroepithelial cell divides vertically. Similarly, in dissociated cell cultures, some retinal neuroepithelial cells divide asymmetrically and distribute Numb to only one of the two daughter cells, suggesting that the dissociated cells can retain their polarity in vitro. Using retinal explant cultures, we find that the retinal pigment epithelium apparently promotes vertical divisions in the neural retina. To our knowledge, this is the first evidence that asymmetric segregation of cell-fate determinants may contribute to cell diversification in the mammalian retina and that an epithelium controls this process by influencing the plane of division in the adjacent neural retina.

Animals↗
PubMed1991

Effects of methylmercury on neuroepithelial germinal cells in the developing telencephalic vesicles of mice.

Methylmercury (MeHg) poisoning (20 mg/kg body weight) in embryonic mice resulted in significant reductions of mitotic indices in the neuroepithelial germinal cells of the telencephalon at the ventricular surface 4 to 12 h following intoxication. After 24 h, no significant difference in the mitotic indices was observed as compared to controls. However, after 48 h there was an increase in mitotic indices of MeHg group as compared to controls. Analysis of the mitotic figures revealed features suggestive of early-phase mitotic arrest in MeHg-exposed animals. Radioautographic studies suggest a disturbance in the interkinetic nuclear migration of proliferating ventricular cells in the MeHg group. Acute degenerative changes in scattered ventricular cells characterized by edema and spongy changes of cytoplasm associated with dissolution of ribosomes, clearing of the cytoplasmic matrix and loss of organelles including microtubules were observed by electron microscopy. Loss of microtubules was also evident within mitotic figures in MeHg-poisoned animals. It is suggested that reduction and arrest of mitotic activity and disturbances in the interkinetic nuclear migration of neuroepithelial germinal cells are related to cytotoxic effects of MeHg on ventricular cells, including effects on microtubules. These findings suggest in that MeHg severely affects proliferating neuroepithelial germinal cells during the acute phases of MeHg poisoning, and that these changes may eventually affect the architectonic makeup of the cortical plate as the brain matures.

Animals↗
PubMed1983

Comparative biology of small granule cells and neuroepithelial bodies in the respiratory system. Short review.

Small granule epithelial cells and clusters of these cells termed neuroepithelial bodies are widely distributed in the respiratory systems of vertebrates, according to observations made in 24 species. The cells are thinly scattered along extrapulmonary and intrapulmonary airways from the larynx to the entrances of the alveoli. As a rule they escape notice unless demonstrated by special light microscopic methods including silver impregnation, PAS-lead hematoxylin staining, or immunocytochemical localization of a marker enzyme, neuron-specific enolase, all of which reveal small granule cells as a class. They are also recognizable in electron micrographs by their characteristic 1,000 to 3,000 A dense-core granules. These can differ in appearance from cell to cell within the same or different species, and small granule cells also can differ in their anatomical relationships or in their content of pharmacological agents like serotonin and peptide hormones bombesin, calcitonin, or leu-enkephalin. Current evidence thus clearly points out the heterogeneity of the class, although it is inadequate to characterize the presumptive endocrine or paracrine function of any of its members specifically. This brief review gives an idea of the range of animals surveyed for small granule cells as well as similarities and differences among cells from different species. It concludes with comments on practical methods for revealing these cells and guidance to sources of detailed information about them.

Animals↗
PubMed1996

Restricted expression of the actin-regulatory protein, tropomyosin, defines distinct boundaries, evaginating neuroepithelium, and choroid plexus forerunners during early CNS development.

In the hindbrain, rhombomeres represent morphological units that develop characteristic, segment-specific structures. Similar segments, known as prosomeres, have been proposed to exist in the forebrain. The neuroepithelial cells of the sharp boundary regions that form the borders between many segments often exhibit distinct shapes, reflecting unique cytoskeletal organization. The present investigation examined the expression of one family of actin-binding, regulatory proteins, the tropomyosins (TM), in boundaries. We found that high molecular weight TMs selectively concentrate in boundary cells and other neuroepithelial zones that exhibit unique cell shapes and movements. Specific TM expression is found at hindbrain boundaries as early as embryonic day 10 in the rat, whereas rhombomeres themselves were TM-negative. Highly restricted TM localization also defined some prosomere boundaries in the early forebrain, particularly those exhibiting unique cell shapes. Furthermore, several regions of the neuroepithelium that evaginate are TM-immunoreactive, including tuberal and preoptic neuroepithelium. Most striking, a subpopulation of neuroepithelial cells in the medial telencephalic wall expresses TM, apparently marking the neuroepithelial region that gives rise to the choroid plexus at least 2 d before its formation. This suggests that the medial cerebral wall is not entirely dedicated to generating cells that comprise allocortex. TM expression in the choroid plexus is maintained through initial evagination and appearance in all ventricles. The spatially restricted expression of TMs implicates that this actin-binding protein is involved in the dynamic regulation of cell shape or motility associated with boundary formation and morphogenesis of the neuroepithelium during critical stages of brain development.

Actins↗
PubMed2003

Radial glia diversity: a matter of cell fate.

Early in development of the central nervous system, radial glial cells arise from the neuroepithelial cells lining the ventricles around the time that neurons begin to appear. The transition of neuroepithelial cells to radial glia is accompanied by a series of structural and functional changes, including the appearance of "glial" features, as well as the appearance of new signaling molecules and junctional proteins. However, not all radial glia are alike. Radial glial lineages appear to be heterogeneous both within and across different brain regions. Subtypes of neurogenic radial glia within the cortex, for example, may have restricted potential in terms of the cell types they are able to generate. Radial glia located in different brain regions also differ in their expression of growth factors, a diverse number of transcription factors, and the cell types they generate, suggesting that they are involved in regionalization of the developing nervous system in several aspects. These findings highlight the important but complex role of radial glia as participants in key steps of brain development.

Animals↗
PubMed1989

The N-ras oncogene is activated in a human medulloblastoma cell line.

Medulloblastoma is a malignant brain tumor of early childhood whose cells resemble the primitive neuroepithelial cells found normally in the developing nervous system. Medulloblastoma may be caused by mutational events affecting primitive neuroepithelial cells and preventing their differentiation into postmitotic neurons. The human ras genes, H-ras, K-ras and N-ras, are members of a family of proto-oncogenes that are targets for mutational changes that convert these normal genes into active, transforming oncogenes. Here we report that the N-ras oncogene is activated in the human medulloblastoma cell line TE 671 by a mutation at the third position of codon 61. A point mutation at this location corresponds to a substitution of histidine for glutamine in the N-ras gene product, p21. The oncogenic activation was shown by focus-formation in NIH 3T3 cell transfection assays. The location of the mutation was established using oligonucleotide hybridization assays enhanced through in vitro amplification of N-ras coding sequences using the Taq polymerase chain reaction. N-ras activation may be one of the mutational events that subvert normal neuroectodermal differentiation and lead to medulloblastoma in children.

Cell Transformation, Neoplastic↗
PubMed1996

[The histogenesis of embryonic neocortical allografts in rats under the action of cyclosporine A].

By means of morphological methods, a study was made of effects of cyclosporin A (Cs A) on developmental dynamics in 15 day old embryo neocortex transplanted into the rat brain. It is shown that Cs A exerts no cytotoxic or cytostatic effects on grafting cells. Differentiation of grafting neuroepithelial cells into neuroblasts, young neurons and neurons in transplants of Cs A-treated rats and control transplants took place at the same time. Mitotic activity of grafting neuroepithelial cells was lower than in developing neocortex in situ; pathological mitotic forms have been described.

Animals↗
PubMed1995

Developmentally regulated vitronectin influences cell differentiation, neuron survival and process outgrowth in the developing chicken retina.

Vitronectin is a multifunctional protein involved in the regulation of the immune system and blood coagulation. Here we report that the expression of vitronectin is developmentally regulated in the embryonic retina of the chicken. Vitronectin immunoreactivity was detected in chicken retinas from embryonic day 5, encompassing the cell bodies of most neuroepithelial cells. At this developmental stage, alpha v integrin subunit expression was distributed across the retina, suggesting a ligand/receptor interaction. Expression of both vitronectin and alpha v increased during development and reached a maximum at embryonic day 9, a time when most differentiated neurons grow processes and initiate synapse formation. At this age, vitronectin immunoreactivity appeared to be located predominantly in the fiber and inner plexiform layers of the differentiated stratified retina. alpha v immunoreactivity and mRNA expression was seen associated with all layers formed by differentiated neurons, being most abundant in the ganglion cell and inner nuclear layers. Later in development, levels of vitronectin decreased and immunoreactivity appeared exclusively associated with the fiber layer. In accordance with this pattern of expression, vitronectin as a substrate sustained both proliferation and differentiation of cultured neuroepithelial cells from embryonic day 5 retinas. At later stages, vitronectin supported survival and neurite outgrowth of most differentiated neurons. Our data suggest that vitronectin is a ubiquitous component of the retinal extracellular matrix, serving as a substrate for developmental processes such as proliferation, differentiation of neuron progenitors, cell survival, and axonal and dendritic growth of differentiated neurons.

Animals↗
PubMed2001

Adherens junctions inhibit asymmetric division in the Drosophila epithelium.

Asymmetric division is a fundamental mechanism for generating cellular diversity. In the central nervous system of Drosophila, neural progenitor cells called neuroblasts undergo asymmetric division along the apical-basal cellular axis. Neuroblasts originate from neuroepithelial cells, which are polarized along the apical-basal axis and divide symmetrically along the planar axis. The asymmetry of neuroblasts might arise from neuroblast-specific expression of the proteins required for asymmetric division. Alternatively, both neuroblasts and neuroepithelial cells could be capable of dividing asymmetrically, but in neuroepithelial cells other polarity cues might prevent asymmetric division. Here we show that by disrupting adherens junctions we can convert the symmetric epithelial division into asymmetric division. We further confirm that the adenomatous polyposis coli (APC) tumour suppressor protein is recruited to adherens junctions, and demonstrate that both APC and microtubule-associated EB1 homologues are required for the symmetric epithelial division along the planar axis. Our results indicate that neuroepithelial cells have all the necessary components to execute asymmetric division, but that this pathway is normally overridden by the planar polarity cue provided by adherens junctions.

Adenomatous Polyposis Coli Protein↗
PubMed1996

Morphological analysis of the early development of the chick neural tube separated from the floor plate and notochord.

When the neural tube of avian embryos is separated from the notochord and floor plate, motoneurons in the spinal cord fail to develop. In order to investigate the factors involved in this phenomenon, cell proliferation activity and cell death were observed following paramedian incision of the neural tube at the level of the segmental plate using colchicine, BrdU, and TUNEL methods. If the notochord and/or floor plate produces a substance(s) that promotes cell division in the basal plate neuroepithelium or that supports the survival of the motoneuron's neuroblasts, mitotic figures should not be present in the neuroepithelium nor should substantial cell death be observed in the ventral aspect of the notochord- and floor plate-deprived neural tube. Surprisingly, however, neither result was observed in the present experiments, with the exception of a considerable amount of homogeneously distributed cell death. Neuroepithelial cells continued to proliferate and gave rise to neuroblasts. Nevertheless, motoneurons failed to develop, and the neural tube was enveloped by only the basement membrane of the alar plate (S. Hirano and H. Tanaka, 1994, Dev. Growth Differ: 36, 481-488). These morphological results revealed that the cause of the development of the anterior horn lacking a neural tube in the notochord- and neural tube-eliminated embryos is not the elimination of the source of the surviving factor(s) of the motoneuron's neuroblasts, but rather the elimination of the signals to induce the motoneurons, derived from the notochord and/or floor plate. The larger amount of cell death in the neural tube on the experimental side suggests that a nonspecific survival factor(s), necessary for the survival of a variety of types of neuroblasts, is also produced by the notochord and/or floor plate.

Animals↗