SEARCH · PubMed Health

Results for “Neurulation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

PubMed1995

Cooperative model of epithelial shaping and bending during avian neurulation: autonomous movements of the neural plate, autonomous movements of the epidermis, and interactions in the neural plate/epidermis transition zone.

Morphogenetic movements during neurulation cause a tissue to change shape within the plane of the epithelium (e.g., conversion of the oval neural plate into the narrow spinal plate and the wide brain plate), cause bending out of the plane of the epithelium (e.g., raise the neural folds and curl the neural plate into a tube), or contribute to both phenomena. In this study, pieces that contain neural plate alone, epidermis alone, or both tissues (with or without underlying tissues) are cut from chick embryos and allowed to develop for up to 24 hr. Examination of histological sections through such isolates allows analysis of the formation of neural folds. When the neural plate/epidermis transition zone is disrupted, neural folds do not form. Conversely, when the transition zone remains intact, neural folds form. Neural folds form even when most of the medial neural plate and lateral epidermis has been removed, leaving only the isolated transition zone. These data indicate that the transition zone is both necessary and sufficient for the formation of neural folds. The transition zone may play a number of roles in epithelial bending including organizing, focussing, and redirecting movements that are autonomous to the neural plate or epidermis. Time-lapse video recording, and sequential photographs allowed the documentation of such movements. Neural plate isolates exhibit autonomous rostrocaudal lengthening and mediolateral narrowing. Isolated strips of epidermis exhibit autonomous movements which, unlike wound-healing movements, are unidirectional (medial), and region-specific (beginning and reaching their greatest extent in the cranial region). Isolated pieces of neural plate or epidermis remain flat instead of bending, providing further evidence that the transition zone is necessary for the formation of neural folds.

Animals↗

PubMed1978

Distribution of surface coat material on fusing neural folds of mouse embryos during neurulation.

Fusing and non-fusing regions of neural folds from mouse embryos were examined during neurulation for the distribution of extracellular macromolecules (surface coats) prior to and at the time of closure. Ruthenium red staining of 10th day ICR/DUB mouse embryos was used to detect the distribution of surface coat material. Light microscopic examination of fusing and non-fusing regions in the midbrain, hindbrain, and spinal cord showed a consistent increase in ruthenium red positive material immediately prior to closure. Heavy deposits of positive staining material were present along apical neural fold borders and overlying ectoderm cells. This staining pattern was consistent in the three regions examined, but the pattern of initial contact between opposing neural folds differed. In mid- and hindbrain areas contact was initiated by overlying ectoderm, whereas in spinal cord regions contact was first established by neuroepithelial cells. Once contact between opposing neural folds was initiated a decrease in stainable material was observed.

Animals↗

PubMed1987

Shaping of the chick neuroepithelium during primary and secondary neurulation: role of cell elongation.

Cell elongation is a cardinal event in formation and shaping of the neuroepithelium during both primary and secondary neurulation. This study had three purposes. The first was to clarify the role of microtubules in maintaining the elongated configurations of chick neuroepithelial cells. Neuroepithelial cells of the neural plate (the rudiment of the primary neural tube) and medullary cord (the rudiment of the secondary neural tube) reduced their heights an average of approximately 25% when their microtubules were depolymerized, but most cells remained considerably elongated and columnar. Complete rounding up occurred only as cells entered metaphase where they arrested. These results suggest that microtubules as well as other factors are required to maintain the fully elongated configurations of cells composing epithelial sheets. The second purpose of this study was to evaluate the hypothesis that neuroepithelial cell elongation plays a major role in narrowing of the neural plate. To do this, the width of the neural plate was examined after microtubule depolymerization and repolymerization. As the heights of neuroepithelial cells decreased with loss of their microtubules, the width of the neuroepithelium increased roughly proportionately; subsequent repolymerization with concomitant cell elongation resulted again in neural plate narrowing. Thus, the hypothesis is supported. The third purpose of this study was to examine the roles of cell rearrangement and change in neuroepithelial cell or extracellular volume in neural plate narrowing and extension. Extensive cell rearrangement, resulting in net cell loss from the width of selected, representative levels of the neural plate, does not seem to play a major role in plate narrowing, but decreases in cell or extracellular volume are likely involved. Further studies are necessary to complete our understanding of the mechanisms driving neural plate shaping and bending.

Animals↗

PubMed1987

Neurulation in the mouse. I. The ontogenesis of neural segments and the determination of topographical regions in a central nervous system.

Ontogenesis of neural segments and positional relationships between the segments and other organs during neurulation were studied in 1,423 ICR mouse embryos by binocular dissecting, light, and scanning electron microscopy. Late in the presomite stage, two transverse sulci, preotic and otic, were seen on the prospective luminal surface of the neural folds. By somite stage 19, the former subdivided into five neuromeres, and by somite stage 21, the latter subdivided into four neuromeres. From the rostral, preotic sulcus, moreover, five other neuromeres were formed by somite stage 20, and between the otic sulcus and the first somite, two neuromeres were formed by somite stage 28. In the caudal part, from the level of the first somite, a total of 39 neuromeres were formed one after another by somite stage 39, and their positions almost correlated with each corresponding somite. Furthermore, the isthmus grew in the boundary between the fifth and sixth neuromere. The most protruding zone in the preotic sulcus formed the eighth neuromere and was located adjacent to the first branchial arch and the trigeminal ganglion. The most protruding zone in the otic sulcus also formed the 11th neuromere and was located adjacent to the second branchial arch. The 12th and 13th neuromeres were situated adjacent to the otic vesicle; the 23rd to 28th neuromeres, adjacent to the forelimb bud; and the 40th to 46th neuromeres, adjacent to the hindlimb bud.

Animals↗

PubMed1989

Neurulation in the mouse: manner and timing of neural tube closure.

The manner and timing of neural fold fusion in primary neurulation were studied in 1,575 normal ICR mouse embryos by using binocular dissecting, light, and scanning electron microscopy. The initial fusion of apposing neural folds occurred at the level of the intermediate point between the third and fourth somites (i.e., in the caudal myelencephalon) and proceeded both rostrally and caudally. A second fusion occurred at what was originally the rostral end of the neural plate and proceeded rostrodorsally. A third fusion occurred in the caudal diencephalon and proceeded both rostrally and caudally. This was followed by complete closure of the telencephalic neuropore at the midpoint of the telencephalic roof and then complete closure of the metencephalic neuropore at the rostral part of the metencephalic roof. A fourth fusion occurred at what was originally the caudal end of the neural plate and proceeded rostrally. Finally, the caudal neuropore completely closed at the level of the caudal end of the future 33rd somite.

Aging↗

PubMed1990

Distribution of cell surface glycoconjugates during secondary neurulation in the chick embryo.

Lectin histochemistry was used to examine the expression of cell surface glycoconjugates during secondary neurulation in chick embryos. Fourteen lectins were applied to serial sections of the caudal region of embryos at the various stages of tail bud development. The lectins Bandeiraea simplicifolia, Dolichos biflorus agglutinin, Phaseolus vulgaris leukoagglutinin, soybean agglutinin, Sophora japonica agglutinin, Ulex europaeus agglutinin and succinylated wheat germ agglutinin (sWGA) showed very light or no binding to the developing medullary cord of the tail bud. With the other lectins, staining occurred throughout the early tail bud and solid medullary cord. During cavitation, however, differential expression of cell surface glycoconjugates by different cell populations was observed. The lectins concanavalin A, Lens culinaris agglutinin, Pisum sativum agglutinin, Phaseolus vulgaris erythroagglutinin, Ricinus communis agglutinin and WGA showed basic similarities in the distribution of lectin binding. Of these, the binding pattern of WGA was the most striking. As the medullary cord cells were separating into central mesenchymal and peripheral epithelial populations, WGA bound preferentially to the epithelial cells and the notochord. The lectin PNA, however, became preferentially bound to the mesenchymal cells. Heavy staining by WGA (specific for N-acetylglucosamine and sialic acid) where sWGA staining (specific for N-acetylglucosamine only) was faint suggested that WGA binding was due to the presence of sialic acid containing glycoconjugates.

Animals↗

PubMed2003

Homocysteine interference in neurulation: a chick embryo model.

BACKGROUND: Periconceptional folic acid supplementation reduces the occurrence and recurrence risk of neural tube defects (NTD). Mothers of children with NTD have elevated plasma homocysteine levels. Administering homocysteine to chick embryos is reported to cause 27% NTD. Therefore, elevated plasma homocysteine levels per se or a disturbed homocysteine metabolism may be teratogenic to the embryo and may interfere with neural tube closure. Our aim was to obtain a chick embryo model to explore the interference of homocysteine in neural tube closure. METHODS: Homocysteine or saline was administered to chick embryos in ovo at 3 hr, 30 hr, and 60 hr of incubation and harvested at 74 hr. Homocysteine was then applied to chick embryos in vitro at a defined time window of four to six somites and followed for 6 hr. RESULTS: Homocysteine administration to chick embryos in ovo resulted in several malformations but not in an increased number of NTDs. Homocysteine administration to chick embryos in vitro resulted in a transient, dose-dependent widening of the anterior neuropore and closure delay of the rhombencephalic neuropore. After 16 hr of incubation the neural tube was closed. CONCLUSIONS: The in vitro chick embryo model appears a good model to explore the interference of a disturbed homocysteine metabolism in neurulation.

Abnormalities, Multiple↗

PubMed1985

Alpha actinin distribution and extracellular matrix products during somitogenesis and neurulation in the chick embryo.

A discrete stage in two different morphogenetic processes has been examined employing fluorescently labelled alpha-actinin as a probe to localize native alpha-actinin and antibodies to localize fibronectin and collagen type I. The stage of somitogenesis examined is the transition from the compact mesenchymal somitic mass to the epithelial somitic vesicle (ie, epithelialization of the somite). The stage of neurulation examined is the transition from the relatively flat neuroepithelium to the approximation of the neural folds. Before these morphogenetic movements begin, the neuroepithelium is sitting upon a basal lamina and interstitial collagen, and the somite is surrounded by a meshwork of interstitial collagen. During both of these processes, the cells become narrowed at their apices in the region of the tissue that is becoming concave, and alpha-actinin is localized in the apices. The localization of intracellular alpha-actinin and extracellular fibronectin, and the distribution of collagen, suggest that there is a coordinated appearance and distribution of these molecules that is temporally associated with these discrete morphogenetic events.

Actinin↗

PubMed2004

Dynamic expression of Lef/Tcf family members and beta-catenin during chick gastrulation, neurulation, and early limb development.

Members of the Lef/Tcf family of HMG-box transcription factors mediate the response to Wnt as part of the canonical Wnt signaling cascade. Positive and negative cofactors, including beta-catenin, CtBP, and Smad3, regulate the activity of Lef/Tcf transcription complexes. Interaction of Lef/Tcfs with beta-catenin results in target gene activation or repression, depending on the context. Here, we report the cloning of a novel chick Tcf-1 splice variant and of a partial cDNA for chick Tcf-3. We describe their expression patterns during early development and have compared them with the expression profiles of Lef-1 and beta-catenin. We found restricted patterns during gastrulation, neurulation, somitogenesis, and early limb development. beta-catenin and Lef/Tcf expression did not always coincide, indicating developmental contexts in which Lef/Tcf proteins may interact with other cofactors and conversely, the areas in which beta-catenin may interact with other coregulators, or be involved in regulating adhesive properties of cells.

Animals↗

PubMed2004

Assembly and remodeling of the fibrillar fibronectin extracellular matrix during gastrulation and neurulation in Xenopus laevis.

Fibronectin, a major component of the extracellular matrix is critical for processes of cell traction and cell motility. Whole-mount confocal imaging of the three-dimensional architecture of the extracellular matrix is used to describe dynamic assembly and remodeling of fibronectin fibrils during gastrulation and neurulation in the early frog embryo. As previously reported, fibrils first appear under the prospective ectoderm. We describe here the first evidence for regulated assembly of fibrils along the somitic mesoderm/endoderm boundary as well as at the notochord/somitic mesoderm boundary and clearing of fibrils from the dorsal and ventral surfaces of the notochord that occurs over the course of a few hours. As gastrulation proceeds, fibrils are restored to the dorsal surface of the notochord, where the notochord contacts the prospective floor plate. As the neural folds form, fibrils are again remodeled as deep neural plate cells move medially. The process of neural tube closure leaves a region of the ectoderm overlying the neural crest transiently bare of fibrils. Fibrils are assembled surrounding the dorsal surface of the neural tube as the neural tube lumen is restored.

Animals↗

PubMed2006

Asymmetric localization of Numb:EGFP in dividing neuroepithelial cells during neurulation in Danio rerio.

In the neural plate and tube of the zebrafish embryo, cells divide with their mitotic spindles oriented parallel to the plane of the neuroepithelium, whilst in the neural keel and rod, the spindle is oriented perpendicular to it. This change is achieved by a 90 degrees rotation of the mitotic spindle. We cloned zebrafish homologues of the gene for the Drosophila cell fate determinant Numb, and analyzed the localization of EGFP fusion proteins in vivo in dividing neuroepithelial cells during neurulation. Whereas Numb isoform 3 and the related protein Numblike are localized in the cytoplasm, Numb isoform 1 is localized to the cell membrane. Time-lapse analyses showed that Numb 1 is distributed uniformly around the cell cortex in dividing cells during plate and keel stages, but becomes localized at the basolateral membrane of some dividing cells during the transition from neural rod to tube. Using in vitro mutagenesis and Numb:EGFP deletion constructs, we showed that the first 196 amino acids of Numb are sufficient for this localization. Furthermore, we found that an 11-amino acid insertion in the PTB domain is essential for localization to the cortex, whereas amino acids 2-12 mediate the basolateral localization in the neural tube stage.

Amino Acid Sequence↗

PubMed1982

Evidence that secondary neurulation occurs autonomously in the chick embryo.

Other investigations have demonstrated that pressure, exerted by fluid contained within the lumen of the closed neural tube, plays an important role in the morphogenesis of cranial regions of chick embryos. In this study, we investigated whether this pressure is involved also in the formation of the secondary portion of the neural tube--the portion formed by canalization of a solid mass of cells. To determine this, the posterior neuropore was prevented from closing (resulting in myeloschisis localized to he lumbosacral region) by removing the portion of the vitelline membrane covering the embryo, and reincubating for various periods. Secondary neurulation occurred normally in embryos exhibiting lumbosacral myeloschisis, demonstrating that this process occurs autonomously in chick embryos. Additional experimental studies are needed to ascertain what specific mechanisms cause the secondary portion of the neural tube to form.

Animals↗

PubMed2002

Quantification and localization of expression of the retinoic acid receptor-beta and -gamma mRNA isoforms during neurulation in mouse embryos with or without spina bifida.

BACKGROUND: Previous studies observed that retinoic acid receptor-gamma (RARgamma) is expressed in the open caudal neuroepithelium but that RARbeta is expressed in the closed neural tube. Furthermore, retinoic acid (RA) induces RARbeta expression, a molecular event associated with neural tube closure, but treatment with RA at the appropriate gestation time causes failure of neural tube closure. Since there are four isoforms of RARbeta, perhaps the isoforms expressed in the closed neural tube and induced by RA are different. To investigate the hypothesis that the switch from RARgamma to RARbeta is mechanistically linked to neural tube closure, this study determined the concentrations and distributions of RARbeta and RARgamma isoforms in mouse embryos with RA-induced neural tube defects and in splotch (Sp) mutant embryos with spina bifida. METHODS: Absolute concentrations of RARbeta and RARgamma isoforms were determined throughout primary neurulation (gestational day 8.5-10.0) in treated or untreated C57BL/6J mouse whole embryos by ribonuclease protection analysis. Treatment consisted of an oral dose of 100 mg/kg of all-trans-RA on gestational day 8.5. Spatial distributions of RARbeta and RARgamma were examined in RA-treated and Sp mutant embryos by in situ hybridization. RESULTS: RARbeta2, gamma1, and gamma2 were expressed in untreated embryos and were induced 4.5-, 1.6-, and 4.0-fold, respectively, 4 hr after treatment with RA. In embryos with RA-induced spina bifida, RARbeta2 was expressed in the closed neural tube while RARgamma1 and RARgamma2 were expressed in the open caudal neuroepithelium. In splotch mice with spina bifida, the boundary between RARbeta and RARgamma did not correspond to the site of neural tube closure. CONCLUSIONS: In RA-treated embryos, the relationship between RARbeta expression in the closed and RARgamma in the open caudal neuroepithelium was not altered. However, in splotch embryos with spina bifida, the juncture between RARbeta and RARgamma expression remained in the same anatomical position in the neuroepithelium irrespective of the neural tube closure status and suggests that the switch from RARgamma to RARbeta expression in the closing caudal neuroepithelium may not be causally linked to neural tube closure in the splotch mutant.

Animals↗

PubMed2001

Inhibitors of choline uptake and metabolism cause developmental abnormalities in neurulating mouse embryos.

BACKGROUND: Choline is an essential nutrient in methylation, acetylcholine and phospholipid biosynthesis, and in cell signaling. The demand by an embryo or fetus for choline may place a pregnant woman and, subsequently, the developing conceptus at risk for choline deficiency. METHODS: To determine whether a disruption in choline uptake and metabolism results in developmental abnormalities, early somite staged mouse embryos were exposed in vitro to either an inhibitor of choline uptake and metabolism, 2-dimethylaminoethanol (DMAE), or an inhibitor of phosphatidylcholine synthesis, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH(3)). Cell death following inhibitor exposure was investigated with LysoTracker Red and histology. RESULTS: Embryos exposed to 250-750 microM DMAE for 26 hr developed craniofacial hypoplasia and open neural tube defects in the forebrain, midbrain, and hindbrain regions. Embryos exposed to 125-275 microM ET-18-OCH(3) exhibited similar defects or expansion of the brain vesicles. ET-18-OCH(3)-affected embryos also had a distended neural tube at the posterior neuropore. Embryonic growth was reduced in embryos treated with either DMAE (375, 500, and 750 microM) or ET-18-OCH(3) (200 and 275 microM). Whole mount staining with LysoTracker Red and histological sections showed increased areas of cell death in embryos treated with 275 microM ET-18-OCH(3) for 6 hr, but there was no evidence of cell death in DMAE-exposed embryos. CONCLUSIONS: Inhibition of choline uptake and metabolism during neurulation results in growth retardation and developmental defects that affect the neural tube and face.

Abnormalities, Drug-Induced↗

PubMed1983

Arsenic-induced exencephaly in the mouse and associated lesions occurring during neurulation.

Early tissue damage following a teratogenic dose of arsenic to the dam was studied in mice with the objective of detecting the primary lesion associated with the development of exencephaly. Animals were killed 6 to 21 h after a single 45 mg/kg intraperitoneal injection of sodium arsenate on day 8 of pregnancy and neurulation-stage embryos were fixed for histological and ultrastructural examination. In the prospective hindbrain, the most consistent feature associated with arsenate treatment was the widely separated neural folds which were not positioned for closure. Intracytoplasmic inclusions, interpreted as necrotic debris, were most numerous in the apical portion of the neural folds, sometimes extending into the mesenchyme, but they were not extensive in most embryos. In the prospective forebrain, necrotic debris was found throughout the neuroepithelium, in contrast to the posterior portions of the developing brain. It is not clear that necrosis of the neuroepithelium or mesenchyme would in itself be the primary lesion associated with exencephaly, although death of specific cells such as those participating in the fusion process could be involved. The potential effect of arsenate on physiological and biochemical processes which could affect neural tube closure is discussed.

Abnormalities, Drug-Induced↗

PubMed1992

Comparison of staging systems for the gastrulation and early neurulation period in rodents: a proposed new system.

Because there is no standard developmental staging system for the early postimplantation period of rodent embryos, investigators must now choose between a variety of systems that differ significantly. We have reviewed many of these staging systems and have summarized the ambiguities within them and the inconsistencies among them. In order to compare systems, we first obtained a consensus of the order of developmental events from the literature, and then attempted to fit existing systems into this order taking into account inconsistencies in terminology and blurred borderlines between stages. We were able to do this for most systems but not all because some were too divergent. We found that inconsistencies in definition of some terms, such as "primitive streak stage" and those used to describe the early neurulation process (neural plate, neural groove, neural folds, and head fold) cause much confusion. In order to develop an unambiguous system which can be used by all investigators, we propose to modify Theiler's system, which is one of the most commonly used systems but is not defined precisely during the early postimplantation period. We suggest making subdivisions of the original stages as follows: 1) stage 8 into 8a and 8b, by the degree of extension of the proamniotic cavity into the extraembryonic region; 2) stage 10 into 10a and 10b, by the completion of amnion formation; 3) stage 11 into 11a, 11b, and 11c, by the appearance of neural folds and foregut pocket. After Stage 12, the number of somite pairs can be used to precisely stage embryos.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Inhibitors of glycolytic metabolism affect neurulation-staged mouse conceptuses in vitro.

In order to evaluate the apparent discordance between altered glucose metabolism and embryonic energy production, the effects of inhibitors of glucose utilization on morphological development and biochemical changes in mouse embryos in culture were evaluated. Day 9 ICR mouse conceptuses having 3-6 pairs of somites were prepared for culture as previously described. 2-Deoxyglucose (2DG) produced a concentration-dependent effect on development. A 25 microM 2DG concentration did not induce neural tube closure defects (NTDs) but 100 microM, 100% of embryos exhibited this defect. A 17% reduction in the rate of lactate production by the conceptus was produced by a 24-hr exposure period to 100 microM 2DG. Iodoacetate, which inhibits glyceraldehyde-3-phosphate dehydrogenase in adult tissues, produced high rates of NTDs at concentrations > or = 2.5 microM. Following a 24 hour exposure to iodoacetate, lactate production was inhibited at 10 and 25 microM. The effects of 2DG on embryonic ATP content were assessed to test the hypothesis that effects on glucose utilization would effect embryonic ATP content. Despite using 2DG concentrations that alter development and inhibit glycolysis, there were no effects on whole embryo or visceral yolk sac (VYS) ATP content. However, when the embryo was divided into regions, there was a specific reduction in ATP content in the head following a 24-hr exposure period. No effect of 2DG on head ATP content was produced after 12 hr of exposure. To determine if there were region specific differences in 2DG uptake and distribution that could account for the differential effects of 2DG on ATP content, 14C-2DG accumulation in different regions of the embryo and VYS was determined over the 24-hr culture period. The uptake of 2DG was dependent on the medium 2DG concentration and suggested a higher accumulation in regions with decreased ATP. However, when the uptake was monitored for a 1-hr period after a 24-hr exposure, there was no region specific differences in 2DG uptake. These studies further document the adverse developmental effects of inhibitors of glucose utilization during the early stage of neurulation. The biochemical mechanism for induction of these defects is unclear, but an effect on ATP content does not appear to be solely responsible for the dysmorphogenesis.

Adenosine Triphosphate↗

PubMed1993

A novel chicken homeobox-containing gene expressed in neurulating embryos.

We have isolated a cDNA clone from chicken embryo that contains a homeobox sequence (CHox-cad2). Analysis at the nucleotide and amino acid levels revealed closest similarity to the Xenopus Xcad1 and to other homeoboxes related to Drosophila caudal. RNA blot analysis showed hybridization of CHox-cad2 to two transcripts of 2.6 and 1.5 kb, present at day 1 of embryogenesis (E1). Using the highly sensitive polymerase chain reaction (PCR) to amplify cDNAs from embryonic RNAs from E0 (unincubated blastoderm) to E4, we confirmed the restricted expression of this homeobox sequence to the period of neurulation (E1).

Amino Acid Sequence↗