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Results for “Neurulation”

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At least 163 records · Page 9Linked to original sources

PubMed1999

Teratogenic response to arsenite during neurulation: relative sensitivities of C57BL/6J and SWV/Fnn mice and impact of the splotch allele.

Arsenic is an environmental contaminant that induces congenital malformations, primarily neural tube defects, in laboratory animals, and it may contribute to human birth defects. The acute doses of arsenicals required to elicit teratogenesis in outbred strains of mice, however, are orders of magnitude higher than those to which humans are exposed environmentally. In order to examine interactions between arsenite administration during neurulation and murine genotype, the present study compares two inbred mouse strains, establishes a teratogenic dose of arsenite, and evaluates the effect of the splotch mutation on arsenic-induced teratogenesis. SWV/Fnn or C57BL/6J females were injected intraperitoneally with sodium arsenite (10 mg/kg) on days 6.5, 7.0, 7.5, 8.0, 8.5, or 9.0 of gestation. A dose-response study was carried out in the C57BL/6J strain, and the effect of the splotch mutation, introduced via the male (C57BL/6J Sp/+), was assessed. Fetuses were examined for external, visceral, and skeletal malformations. Fetuses from crosses of C57BL/6J females with C57BL/6J Sp/+ males were genotyped by PCR. Ten-mg/kg sodium arsenite was teratogenic in nearly 50% of C57BL/6J fetuses, and the C57BL/6J strain was significantly more sensitive to arsenite-induced embryo-lethality and teratogenicity than the SWV/Fnn strain. The spectrum of malformations produced was dependent on the gestational time point of arsenite administration. Introduction of the splotch allele significantly increased neural tube defects and other specific malformations. This result demonstrates that a mutation in a single gene can increase sensitivity to arsenic-induced birth defects. This murine study examines the interaction between arsenite-induced teratogenicity and genotype.

Abnormalities, Drug-Induced↗

PubMed1997

Mice lacking the ski proto-oncogene have defects in neurulation, craniofacial, patterning, and skeletal muscle development.

The c-ski proto-oncogene has been implicated in the control of cell growth and skeletal muscle differentiation. To determine its normal functions in vivo, we have disrupted the mouse c-ski gene. Our results show a novel role for ski in the morphogenesis of craniofacial structures and the central nervous system, and confirm its proposed function as a player in skeletal muscle development. Homozygous mutant mice show perinatal lethality resulting from exencephaly, a defect caused by failed closure of the cranial neural tube during neurulation. The timing of the neural tube defect in ski -/- embryos coincides with excessive apoptosis in the cranial neuroepithelium, as well as in the cranial mesenchyme. Homozygous ski mutants also exhibit a dramatic reduction in skeletal muscle mass, consistent with a defect in expansion of a myogenic precursor population. Nestin is an intermediate filament expressed in highly proliferative neuroepithelial stem cells and in myogenic precursors. Interestingly, we find decreased nestin expression in both the cranial neural tube and the somites of ski -/- embryos, compared with their normal littermates, but no reduction of nestin in the caudal neural tube. These results are consistent with a model in which ski activities are required for the successful expansion of a subset of precursors in the neuroepithelial or skeletal muscle lineages.

Animals↗

PubMed1993

Effects of altered maternal metabolism during gastrulation and neurulation stages of embryogenesis.

In summary, many congenital malformations are produced during gastrulation and neurulation stages of embryogenesis at a time when no definitive chorioallantoic placenta has been established. In rodents, altered maternal metabolism may have a direct impact on the embryo or an indirect impact via disruption of the nutritive function of the visceral yolk sac. If similar mechanisms operate in human embryos, these factors probably alter functions of the trophoblastic shell. In any case, it is crucial to remember that the metabolic status of the embryo is rapidly changing and during early stages of organogenesis may respond to alterations in nutrients quite differently during the first four weeks of gestation than at later stages of organogenesis and the fetal period.

Amino Acids↗

PubMed1986

Stereological analysis of ultrastructural changes of surrounding tissues to neuroectoderm during chick embryo neurulation.

The cytometric evolution of different subcellular components in the epiblast and the mesoderm of chick embryo during neurulation has been studied with stereological methods. The coefficient of cellular form (CFc) has specific values for each type, the epiblast having a mean CFc of 0.474, while the mesoderm, which has ellipsoidal cells, has a mean CFc of 0.643. The nucleus does not show any change of its coefficient of form although its surface density increases significantly. The proportion of mitochondria, present in the cells of each embryonic layer, remains constant during the 4 stages, being higher in the mesoderm cells (epiblast 3.6%; mesoderm 4.3%). The epiblast cells show a stable vitelline reserve, though the relative proportions of lipid bodies and yolk droplets vary: the volume density of yolk droplets increases from stage 5 (3.1%) to stage 8 (7.7%), while the lipid bodies diminish from 7 to 3.6% during this period. The mesoderm cells undergo a remarkable loss of vitelline volume during the same period. The rough endoplasmic reticulum of each cellular type has a remarkable length density increase, the significance of which is discussed in relation to production of extracellular matrix.

Animals↗

PubMed1988

Stereological study of the early ultrastructural differentiation of chick embryo neuroepithelial cells during neurulation.

The neuroectodermal cells of chick embryos have been analyzed during neurulation by stereological and morphometrical ultrastructural methods in an attempt to describe their cytometric evolution. A profound change of cellular form coefficient was observed which is related to the typical process of columnarization of these cells. At stages 7 and 8, the nucleus appeared round in shape, probably due to a loss of pressure of the vitelline inclusions. In this sense, the volume density of these inclusions falls during this period. There was also a significant increase of the nuclear surface density, the significance of which is discussed on the basis of the nucleo-cytoplasmic interchanges and the differentiation process. At the same time, an increase in the number of mitochondria was observed, which is related to the neural folding process. Simultaneously, the amount of rough endoplasmic reticulum increases, presumably related to the remarkable changes of the embryonic extracellular matrix.

Animals↗

PubMed2004

Inhibition of the cell cycle is required for convergent extension of the paraxial mesoderm during Xenopus neurulation.

Coordination of morphogenesis and cell proliferation is essential during development. In Xenopus, cell divisions are rapid and synchronous early in development but then slow and become spatially restricted during gastrulation and neurulation. One tissue that transiently stops dividing is the paraxial mesoderm, a dynamically mobile tissue that forms the somites and body musculature of the embryo. We have found that cessation of cell proliferation is required for the proper positioning and segmentation of the paraxial mesoderm as well as the complete elongation of the Xenopus embryo. Instrumental in this cell cycle arrest is Wee2, a Cdk inhibitory kinase that is expressed in the paraxial mesoderm from mid-gastrula stages onwards. Morpholino-mediated depletion of Wee2 increases the mitotic index of the paraxial mesoderm and this results in the failure of convergent extension and somitogenesis in this tissue. Similar defects are observed if the cell cycle is inappropriately advanced by other mechanisms. Thus, the low mitotic index of the paraxial mesoderm plays an essential function in the integrated cell movements and patterning of this tissue.

Animals↗

PubMed2006

N-cadherin is required for the polarized cell behaviors that drive neurulation in the zebrafish.

Through the direct analysis of cell behaviors, we address the mechanisms underlying anterior neural tube morphogenesis in the zebrafish and the role of the cell adhesion molecule N-cadherin (N-cad) in this process. We demonstrate that although the mode of neurulation differs at the morphological level between amphibians and teleosts, the underlying cellular mechanisms are conserved. Contrary to previous reports, the zebrafish neural plate is a multi-layered structure, composed of deep and superficial cells that converge medially while undergoing radial intercalation, to form a single cell-layered neural tube. Time-lapse recording of individual cell behaviors reveals that cells are polarized along the mediolateral axis and exhibit protrusive activity. In N-cad mutants, both convergence and intercalation are blocked. Moreover, although N-cad-depleted cells are not defective in their ability to form protrusions, they are unable to maintain them stably. Taken together, these studies uncover key cellular mechanisms underlying neural tube morphogenesis in teleosts, and reveal a role for cadherins in promoting the polarized cell behaviors that underlie cellular rearrangements and shape the vertebrate embryo.

Animals↗

PubMed1988

Origin of the dorsal surface of the neural tube by progressive delamination of epidermal ectoderm and neuroepithelium: implications for neurulation and neural tube defects.

Knowledge of the morphogenetic events involved in the development of the dorsal portion of the neural tube is important for understanding neural tube closure, neural crest cell formation and emigration, and the origin of neural tube defects. Here, I characterize the progressive development of the tips of the neural folds during fold elevation in the trunk of mouse and chick embryos and the events leading to formation of the dorsal portion of the neural tube as the epidermal ectoderm (EE) and neuroepithelium (NE) separate from each other. The nature and timing of appearance of collagen IV, laminin and fibronectin were analysed by immunofluorescent and immunogold labelling, and ruthenium red and tannic acid were used to enhance staining for proteoglycans and glycosaminoglycans. As the neural folds elevate, the NE and EE delaminate progressively beginning at the basal surface of the lateral extremes of the neural plate. Nevertheless, the two epithelia remain connected across the zone of delamination by their previously existing basal laminae. In each fold, proteoglycan granules appear at the interface between the NE and EE before delamination begins, and then an (interepithelial) space begins to open and propagate dorsally. Other extracellular matrix (ECM) molecules appear within the space a short distance behind its tip and basal lamina deposition begins shortly thereafter. As fusion occurs, the interepithelial spaces of the two folds coalesce and the final separation of the EE from the NE is accomplished. These observations suggest that the previously recognized delay in deposition of ECM and basal lamina on the dorsal portion of the neural tube and on the overlying EE is a direct consequence of the delamination of the two epithelia and the establishment of two new basal surfaces. The observation that the surface of the dorsal third of the neural tube forms by delamination rather than by juxtaposition of previously existing basal surfaces of the two epithelial is discussed in terms of possible implications for models of neurulation and the origin of neural tube defects.

Animals↗

PubMed1988

Prevention of spinal neural tube defects in the mouse embryo by growth retardation during neurulation.

Homozygous mutant curly tail mouse embryos developing spinal neural tube defects (NTD) exhibit a cell-type-specific abnormality of cell proliferation that affects the gut endoderm and notochord but not the neuroepithelium. We suggested that spinal NTD in these embryos may result from the imbalance of cell proliferation rates between affected and unaffected cell types. In order to test this hypothesis, curly tail embryos were subjected to influences that retard growth in vivo and in vitro. The expectation was that growth of unaffected rapidly growing cell types would be reduced to a greater extent than affected slowly growing cell types, thus counteracting the genetically determined imbalance of cell proliferation rates and leading to normalization of spinal neurulation. Food deprivation of pregnant females for 48 h prior to the stage of posterior neuropore closure reduced the overall incidence of spinal NTD and almost completely prevented open spina bifida, the most severe form of spinal NTD in curly tail mice. Analysis of embryos earlier in gestation showed that growth retardation acts by reducing the incidence of delayed neuropore closure. Culture of embryos at 40.5 degrees C for 15-23 h from day 10 of gestation, like food deprivation in vivo, also produced growth retardation and led to normalization of posterior neuropore closure. Labelling of embryos in vitro with [3H]thymidine for 1 h at the end of the culture period showed that the labelling index is reduced to a greater extent in the neuroepithelium than in other cell types in growth-retarded embryos compared with controls cultured at 38 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Sex difference in mouse embryonic development at neurulation.

Sixty-seven mouse embryos from 10 litters collected on the morning of Day 9 of gestation, when neurulation is beginning, were classified according to the precise stage of development reached, and sex-chromatin analysis was performed on the yolk sac. Within litters, the least developed embryos were more likely to be female than male, while the most advanced embryos were predominantly male. Taking all embryos, the mean somite number was greater in males than females.

Animals↗

PubMed1998

Cloning of a cDNA for xDOR2, a novel TR2-related nuclear orphan receptor, expressed during neurulation in Xenopus laevis embryos.

We isolated from neurulating Xenopus laevis (X. laevis) embryos a cDNA encoding a novel nuclear orphan receptor, Developmental Orphan Receptor 2 (xDOR2), closely related to Ambystoma mexicanum DORI (aDOR1) and to Testicular Receptor-2 (TR2) orphan receptor family members. The xDOR2 cDNA sequence which is truncated both at its 5' and 3' ends predicts a protein sequence of 542 amino acids. While the DNA-binding domain of xDOR2 shares 91%, and 92%, identity with those of aDOR1 and the TR2s, respectively, considerable divergence is observed at both extremities of the peptides. At the N-terminus, xDOR2 is 66% identical to aDOR1 and 64% to the TR2s. At the C-terminus, xDOR2 which is longer by 126 amino acids compared to aDOR1, shares 62%, identity with aDOR1 and appears to contain a complete ligand-binding domain. The DOR receptors appear to form a subtype distinct from the TR2s, and may play a role in the development and differentiation of neural tissues.

Amino Acid Sequence↗

PubMed2000

Complete lack of NF-kappaB activity in IKK1 and IKK2 double-deficient mice: additional defect in neurulation.

NF-kappaB activity is induced by cytokines, stress, and pathogens. IKK1 and IKK2 are critical IkappaB kinases in NF-kappaB activation. In this study mice lacking IKK1 and IKK2 died at E12. Additional defect in neurulation associated with enhanced apoptosis in the neuroepithelium was also observed. MEF cells from IKK1(-/-)/IKK2(-/-) embryos did not respond to NF-kappaB inducers. Upon crossing with kappaB-lacZ transgenic mice, double-deficient embryos also lost lacZ transgene expression in vascular endothelial cells during development. Our data suggest that IKK1 and IKK2 are essential for NF-kappaB activation in vivo and have an important role in protecting neurons against excessive apoptosis during development.

Alleles↗

PubMed1992

Delamination of neuroepithelium and nonneural ectoderm and its relation to the convergence step in chick neurulation.

We have analysed the characteristics of the neuroectoderm-nonneural ectoderm meeting point at several axial levels in relation to the mechanics of neurulation in each level. The results show wide differences at cephalic and somitic levels. At cephalic levels, where convergence plays an important role, the delamination process appears at the beginning of the convergence step. This phenomenon produces a major isolation of the basal lamina, forming a space between this structure and the epithelial sheet in whose basal surface a new basal lamina begins to form. This cavity contains abundant extracellular matrix stained with ruthenium red (RR) and tannic acid (TA), and its increase in volume correlates with the progressive convergence of neural folds. At somitic levels, where the convergence is not important, delamination involves the progressive formation of a half-moon-shaped cavity. This structure appears between a dorsal attachment point, in the tip of neuroectodermal wall, and a ventral attachment point which coincides with the point of bending that determines the bilateral furrow, if it exists. In this small cavity, delamination is not related to an isolation of basal lamina. The RR-staining of the extracellular matrix in this cavity is scarce and the volume increase is smaller than in the cephalic region. These results are discussed in terms of neural fold convergence and neural tube closure.

Animals↗

PubMed1975

[Neurulation and interkinetic nuclear migration in the chick embryo (author's transl)].

Neurulation and interkinetic nuclear migration was studied in cells of the forming neural tube of chick embryos submitted to a variety of treatments. Our results show that cytochalasin B (5 mug/ml) does not protect microtubules against disruption occurring after 3 h at 2 degrees C nor does it prevent their repolymerization once they are cold-disrupted. However, db-cAMP protects microtubules against such cold disruption. We indicate that the inhibitory effect of cytochalasin B on interkinetic nuclear migration cannot be ascribed to an effect on microtubules.

Animals↗

PubMed1986

The distribution of fibronectin, laminin and entactin in the neurulating rat embryo studied by indirect immunofluorescence.

This paper forms part of our study of the extracellular matrix and its role in the morphogenesis of the brain during the period of neurulation in the rat embryo. Using indirect immunofluorescence with polyclonal antibodies, we present here a descriptive study of the distribution of the matrix glycoproteins fibronectin, laminin and entactin. The observed distribution of the fibronectin matrix implicates it in providing a structural element in several morphologically active sites; in addition our observations support the previously suggested involvement of fibronectin in the migration of neural crest cells. Entactin was present only in the basement membranes in conjunction with laminin which was not itself confined to these regions. Laminin was also identified within the mesenchymal extracellular matrix, and its general distribution confirms the previously documented role of laminin in maintaining epithelial structure and organization. No patterning in the distribution of these three glycoproteins could be correlated with the change in shape of the neural epithelium associated with either tube formation or neuromere morphogenesis.

Animals↗

PubMed1986

SEM observations of the neural fold associated with neurulation in the rat.

The topography of the ectoderm was examined by scanning electron microscopy during neurulation in rat embryos at stage 24 (somites 8-11). A zone of altered cell morphology was observed along the crest of neural folds. This zone was located between the presumptive neural tube and the surface ectoderm and exhibited numerous rounded cell blebs, immediately prior to fusion between the folds. It is suggested that the observed surface alterations may reflect a change in the properties of the altered cell which correlate with initial adhesion between the folds.

Animals↗

PubMed1985

A review of the theories of vertebrate neurulation and their relationship to the mechanics of neural tube birth defects.

All of the published theories of neurulation, (some of them forgotten but never disproved), are reviewed for the purpose of assessing just where we are in coming to a satisfactory explanation of this critical step in the formation of the brain and spinal cord, whose occasional failure leads to neural tube birth defects. A new approach to evaluating these theories is introduced, namely finite element analysis, along with a discussion of its promise and present limitations.

Ambystoma↗

PubMed1985

The kinetic behaviour of the cranial neural epithelium during neurulation in the rat.

The kinetic behaviour of the cranial neuroepithelial cells of rat embryos during neurulation is described. Serial transverse sections of 4-, 8-, 12- and 16-somite-stage embryos show that differential mitosis does not play a part in the mechanisms responsible for effecting cranial neural tube closure. A constant cell number is found in the midbrain/hindbrain neural epithelium during all four stages; the mitotic spindle axes are oriented parallel to the long axis of the embryo, so that increase in cell number occurs in this direction only. Growth is only expressed by an expansion in the volume of the forebrain, which projects rostral to the notochordal tip. [3H]thymidine studies (using an in vitro culture technique) show no significant variation in the cell cycle time between the forebrain and the midbrain/anterior hindbrain neural epithelium. It is suggested that the neural epithelium is a fluid structure whose overall shape is strictly controlled while the cells within it flow towards and into the rapidly expanding forebrain.

Animals↗