scholarly journals Abstracts of papers presented at the sixteenth Genetics Society's Mammalian Genetics and Development Workshop held at the Institute of Child Health, University College London on 21 and 22 November 2005

2006 ◽  
Vol 88 (1) ◽  
pp. 67-76 ◽  
Author(s):  
ANDREW J. COPP ◽  
ELIZABETH M. C. FISHER
Keyword(s):  
Neural Tube ◽  
Epithelial To Mesenchymal Transition ◽  
The Body ◽  
Neural Tube Closure ◽  
Mesenchymal Transition ◽  
Mouse Mutants ◽  
Mechanical Tensions ◽  
University College London ◽  
Hinge Points ◽  
Tube Closure

Prior to cranial neural tube closure, the neural folds adopt a biconvex morphology which is thought to be due to expansion of the underlying mesenchyme. Dorso-lateral hinge points (DLHPs) then form, which allow the dorsal tips of the neural folds to ‘flip around’ resulting in apposition of the tips and facilitating subsequent fusion. Cranial closure is particularly prone to perturbation, leading to exencephaly in many mouse mutants and as a result of a variety of teratogenic influences. This may reflect mechanical tensions affecting the closing cranial neural folds. For example, the presence of ventral flexures of the body axis at the mid- and forebrain levels mechanically opposes the formation of DLHPs. Several processes have been implicated as important in overcoming these mechanical tensions, thereby assisting in cranial neural tube closure. These include contraction of actin microfilaments at the luminal surface of the neuroepithelium and apoptosis in the dorsal and dorsolateral neuroepithelium. The latter may act to increase flexibility in the dorsal neural folds, enhancing DLHP formation. Neural crest cells (NCC) originate in the dorsal tips of the neuroepithelium and undergo an epithelial-to-mesenchymal transition, allowing them to delaminate, exit the neuroepithelium and migrate extensively throughout the embryo to form numerous derivatives. We hypothesized that delamination of the NCC from the neuroepithelium may enhance the mechanical flexibility of the dorsal tips of the neural folds, allowing the ‘flip around’ event to occur.

Curvature of the caudal region is responsible for failure of neural tube closure in the curly tail (ct) mouse embryo

Development ◽  
1991 ◽  
Vol 113 (2) ◽  
pp. 671-678 ◽  
Author(s):  
F.A. Brook ◽  
A.S. Shum ◽  
H.W. Van Straaten ◽  
A.J. Copp
Keyword(s):  
Neural Tube ◽  
Mouse Embryo ◽  
Mouse Embryos ◽  
The Body ◽  
Neural Tube Closure ◽  
Posterior Neuropore ◽  
Curly Tail ◽  
Delayed Closure ◽  
Tube Closure

Delayed closure of the posterior neuropore (PNP) occurs to a variable extent in homozygous mutant curly tail (ct) mouse embryos, and results in the development of spinal neural tube defects (NTD) in 60% of embryos. Previous studies have suggested that curvature of the body axis may delay neural tube closure in the cranial region of the mouse embryo. In order to investigate the relationship between curvature and delayed PNP closure, we measured the extent of ventral curvature of the neuropore region in ct/ct embryos with normal or delayed PNP closure. The results show significantly greater curvature in ct/ct embryos with delayed PNP closure in vivo than in their normal littermates. Reopening of the posterior neuropore in non-mutant mouse embryos, to delay neuropore closure experimentally, did not increase ventral curvature, suggesting that increased curvature in ct/ct embryos is not likely to be a secondary effect of delayed PNP closure. Experimental prevention of ventral curvature in ct/ct embryos, brought about by implantation of an eyelash tip longitudinally into the hindgut lumen, ameliorated the delay in PNP closure. We propose, therefore, that increased ventral curvature of the neuropore region of ct/ct embryos imposes a mechanical stress, which opposes neurulation and thus delays closure of the PNP. Increased ventral curvature may arise as a result of a cell proliferation imbalance, which we demonstrated previously in affected ct/ct embryos.

scholarly journals Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies

2018 ◽  
Vol 6 (3) ◽  
pp. 22 ◽  
Author(s):  
Diana Juriloff ◽  
Muriel Harris
Keyword(s):  
Neural Tube ◽  
Gene Mutations ◽  
Neural Tube Closure ◽  
Specific Gene ◽  
New Developments ◽  
Mouse Mutants ◽  
Folate Pathway ◽  
Tube Closure ◽  
Anterior Posterior

The human neural tube defects (NTD), anencephaly, spina bifida and craniorachischisis, originate from a failure of the embryonic neural tube to close. Human NTD are relatively common and both complex and heterogeneous in genetic origin, but the genetic variants and developmental mechanisms are largely unknown. Here we review the numerous studies, mainly in mice, of normal neural tube closure, the mechanisms of failure caused by specific gene mutations, and the evolution of the vertebrate cranial neural tube and its genetic processes, seeking insights into the etiology of human NTD. We find evidence of many regions along the anterior–posterior axis each differing in some aspect of neural tube closure—morphology, cell behavior, specific genes required—and conclude that the etiology of NTD is likely to be partly specific to the anterior–posterior location of the defect and also genetically heterogeneous. We revisit the hypotheses explaining the excess of females among cranial NTD cases in mice and humans and new developments in understanding the role of the folate pathway in NTD. Finally, we demonstrate that evidence from mouse mutants strongly supports the search for digenic or oligogenic etiology in human NTD of all types.

Spinal congenital dermal sinus with dual ostia

2009 ◽  
Vol 3 (5) ◽  
pp. 407-411 ◽  
Author(s):  
Chang Sub Lee ◽  
Ji Hoon Phi ◽  
Seung-Ki Kim ◽  
Byung-Kyu Cho ◽  
Kyu-Chang Wang
Keyword(s):  
Clinical Features ◽  
Neural Tube ◽  
Complete Removal ◽  
The Body ◽  
Neural Tube Closure ◽  
Dermal Sinus ◽  
Spinal Level ◽  
Lumbosacral Lipoma ◽  
Congenital Dermal Sinus ◽  
Tube Closure

Object Congenital dermal sinus (CDS) usually develops in the midline of the body as a single tract. To date, only a few patients with multiple CDS tracts and ostia have been reported. The authors analyzed the clinical features of patients with spinal CDS and multiple ostia and proposed a novel hypothesis for the pathogenesis of the atypical CDS. Methods Five patients with spinal CDS and multiple ostia were included. The clinical, radiological, and operative features of these patients were reviewed retrospectively. Results Three patients demonstrated bilateral paramedian ostia at the same or a very similar spinal level. One patient showed a paramedian and a midline ostium. One patient had 2 unilateral paramedian ostia at different spinal levels. The layers of the internal ending of CDS tracts were diverse. Complete removal of the tracts was possible in all patients. Two patients had dermoid tumors. All patients had an associated anomaly, such as a lumbosacral lipoma or the Currarino triad. The authors propose a “zipping error” hypothesis for the formation of dual ostia located at the spinal level of primary neurulation. An associated anomaly such as a lumbosacral lipoma may contribute to the formation of dual ostia. Conclusions Unilateral or bilateral dual ostia may be present in patients with CDS, especially when an associated anomaly is present. The atypical CDS may develop from aberrant neural tube closure.

scholarly journals Grainyhead-like 2 in development and cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769837 ◽  
Author(s):  
Lijun Ma ◽  
Hongli Yan ◽  
Hui Zhao ◽  
Jianmin Sun
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Neural Tube Closure ◽  
Epithelial Morphogenesis ◽  
Cell Junction ◽  
Mesenchymal Transition ◽  
Barrier Formation ◽  
Regulation Network ◽  
Insight Into ◽  
Tube Closure ◽  
Junction Proteins

Grainyhead-like 2 is a human homolog of Drosophila grainyhead. It inhibits epithelial-to-mesenchymal transition that is necessary for cell migration, and it is involved in neural tube closure, epithelial morphogenesis, and barrier formation during embryogenesis by regulation of the expression of cell junction proteins such as E-cadherin and vimentin. Cancer shares many common characters with development such as epithelial-to-mesenchymal transition. In addition to its important role in development, grainyhead-like 2 is implicated in carcinogenesis as well. However, the reports on grainyhead-like 2 in various cancers are controversial. Grainyhead-like 2 can act as either a tumor suppressor or an oncogene with the mechanisms not well elucidated. In this review, we summarized recent progress on grainyhead-like 2 in development and cancer in order to get an insight into the regulation network of grainyhead-like 2 and understand the roles of grainyhead-like 2 in various cancers.

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