Neurulation abnormalities secondary to altered gene expression in neural tube defect susceptible splotch embryos

Bennett, Gregg; An, Jie; Craig, Johanna C.; Gefrides, Lisa A.; Calvin, James A.; Finnell, Richard H.

doi:10.1002/(sici)1096-9926(199801)57:1<17::aid-tera4>3.0.co;2-4

Cited by 18 publications

(4 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Members of the Pax family are able to suppress apoptosis and upregulate the expression of bcl-2 in embryonic renal cells (Hewitt et al 1997), and of bcl xl in tumor cells (Margue et al 2000). There is also circumstantial evidence that Pax3 and bcl-2 interact during neural tube closure (Bennett et al 1998), suggesting that pax could be involved in the regulation of bcl-2 levels during somite cell death. The blot is quantified and shows that although the 80-kDa cleavage fragment of PARP is elevated in the region of the ablation, PARP is cleaved throughout the somites of the trunk Fig.…”

Section: Discussionmentioning

confidence: 99%

Ablation of axial structures activates apoptotic pathways in somite cells of the chick embryo

Sanders

Parker

2001

Anatomy and Embryology

View full text Add to dashboard Cite

It has been known for some time that ablation of the neural tube and/or the notochord in the chick embryo leads to a massive wave of cell death in the adjacent somites. It is postulated that in the normal embryo, survival signals emanate from the neural tube and/or notochord that suppress apoptosis in the cells of the somites, except for a small population of sclerotome cells that are programmed to die naturally. In this study we show that axial ablation results in the death of sclerotome and not somitic neural crest cells, and we have examined the apoptotic response of these cells to the ablation. We show that several elements of the apoptotic cascade become detectable in somite cells in response to the withdrawal of survival signals. We demonstrate the down-regulation of bcl-2 protein in the somites adjacent to, and caudal to, the site of ablation, corresponding to the region that displays an elevated level of cell death. Although caspase-9 appeared to be activated in somites at all levels of the trunk, caspase-2 showed a clear response to the ablation of the axial structures. Removal of the neural tube and notochord produced an up-regulation of caspase-2 activity in somites in the region of the operation. Cleavage of two down-stream substrates of these caspases was examined. The cleavage of poly (ADP-ribose) polymerase (PARP) was apparent in somites at all levels of the trunk, and showed only a modest up-regulation after ablation. By contrast, the cleavage of DNA fragmentation factor (DFF45) showed a marked up-regulation in response to ablation, suggesting that this is a primary substrate for a caspase-dependent apoptotic mechanism. Evidence was also found for a caspase-independent mechanism, since the expression of apoptosis-inducing factor (AIF) was found to be very sensitive to, and up-regulated in somites by, axial ablation. Because the wave of apoptosis that is precipitated in somites by removal of the axial structures may be mediated by BMP-4, we examined the levels of BMP-4 in somites in response to axial ablation. BMP-4 expression was clearly up-regulated in somites adjacent to, or close to, the site of operation.

show abstract

Section: Discussionmentioning

confidence: 99%

Ablation of axial structures activates apoptotic pathways in somite cells of the chick embryo

Sanders

Parker

2001

Anatomy and Embryology

View full text Add to dashboard Cite

show abstract

“…Overexpression or aberrant regulation of the Pax3 gene can transform fibroblasts into tumor cells in nude mice (12,13), suggesting that this gene may act as a proto-oncogene. Changes in the amount of polysialic acid on NCAM are related to invasive and metastatic growth potential of human tumors (37,39,40) and linked to the modulation of adhesive properties of NCAM. Highly polysialylated NCAM is a cell surface marker for medulloblastoma (41-43), neuroblastoma, and rhabdomyosarcoma (42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Murine Pax3 Increases NCAM Polysialylation in a Human Medulloblastoma Cell Line

Mayanil¹,

George²,

Mania-Farnell³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Along the anterior-posterior axis of the neural tube, Pax3 expression ultimately extends from the diencephalon caudally throughout the spinal cord [44,114]. Expression levels in the neural tube have been reported to be highest immediately prior to fusion of the neural folds and rapidly downregulated following neural tube closure [21].…”

Section: Pax3 In Developmentmentioning

confidence: 99%

Pax3 and the Splotch Mutations: Structure, Function, and Relationship to Teratogenesis, Including Gene-Chemical Interactions

Machado¹,

Martin²,

Collins³

2001

CPD

View full text Add to dashboard Cite

The current review focuses on the malformations resulting from mutations in Pax3 and the interactions of Pax3 mutations with chemically induced teratogenesis, as well as other mutant genes or genetic strains, as a paradigm to illustrate the connections among genetics, protein function, and teratology. Splotch mice result from various mutations involving Pax3, and Waardenburg syndromes I and III in the human are due to mutations in PAX3. The human and murine phenotype/genotype correlations are thus compared and contrasted. The role of Pax3 in normal development, as well as the regulation of Pax3 expression and DNA binding, are also addressed on the premise that a mechanistic understanding of normal developmental processes is prerequisite to full comprehension of the mechanisms by which abnormal development is induced. Pax3 encodes a transcription factor involved in myogenesis, melanogenesis and neurogenesis, as well as regulating genes that may be involved in other cellular processes. The primary goal of this review is to examine the role of a single important developmental gene in the interaction of genetics and abnormal development.

show abstract

Neurulation abnormalities secondary to altered gene expression in neural tube defect susceptible splotch embryos

Cited by 18 publications

References 60 publications

Ablation of axial structures activates apoptotic pathways in somite cells of the chick embryo

Ablation of axial structures activates apoptotic pathways in somite cells of the chick embryo

Overexpression of Murine Pax3 Increases NCAM Polysialylation in a Human Medulloblastoma Cell Line

Pax3 and the Splotch Mutations: Structure, Function, and Relationship to Teratogenesis, Including Gene-Chemical Interactions

Contact Info

Product

Resources

About