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- W756633411 abstract "Neural crest cells are a transient population of pluripotent cells unique to vertebrateembryos. Their importance in vertebrate development is highlighted by the diversity oftheir final fates, which include cells forming the cranialfacial cartilage, the peripheralnervous system, and melanocytes, amongst others. Neural crest cells maintainpluripotency until after they delaminate from the surrounding epithelium and migrate totheir sites of final differentiation. This multi-step process allowing neural crestdelamination and migration is known as epithelial-mesenchymal transition (EMT). Keymolecular events of EMT include the downregulation of E-cadherin and upregulation ofmany transcription factors, including Snail and Slug. Snail and Slug are key regulatorsof EMT, and they are also markers for neural crest identity. This intimate link betweenneural crest fate and EMT provides a system whereby cell fate specification and EMTcan be studied together.Many signalling pathways are known to affect neural crest induction and EMT.However, the molecular details of how these signals mediate this developmentalprogram are poorly understood. I have carried out an overexpression screen in Xenopuslaevis embryos to look for factors affecting neural crest induction and identified severalnovel candidates of interest. Included in the hits identified in the screen are knowngenes that have already been implicated in neural crest induction, which validates thescreen. After some preliminary experiments, I focused my studies on a regulator ofgene expression, SNW domain-containing 1 (SNW1). I discovered that SNW1regulates the BMP gradient in Xenopus embryos responsible for dorsal-ventralpatterning. Manipulation of SNW1 protein level in whole embryos alters the BMPgradient so that the graded response responsible for patterning the ectoderm isdisrupted, with severe consequences for neural crest induction. Two downstreamtargets of SNW1 were identified using microarray analysis and these may mediate theeffect of SNW1 on the BMP gradient, and they may also have direct effects on neuralcrest induction.Neural crest cells undergo EMT to migrate to their final sites of differentiation,and require transcription factors of the Snail family to drive this process. This isreminiscent of cases of EMT observed in some metastatic cancer cells. Loss of SNW1prevents neural crest induction and expression of Snail, hence SNW1 may play animportant role in cancer progression as well." @default.
- W756633411 created "2016-06-24" @default.
- W756633411 creator A5042855170 @default.
- W756633411 date "2009-12-01" @default.
- W756633411 modified "2023-09-28" @default.
- W756633411 title "Factors required for neural crest induction in Xenopus laevis embryos: from screening to characterisation" @default.
- W756633411 hasPublicationYear "2009" @default.
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