Using stage-specific over-expression in transgenic <i>Xenopus</i> embryos, I show that both Wnt6 and β-catenin can negatively regulate several molecular markers for heart muscle differentiation as well as earlier heart-specific transcription factors. In addition, Wnt6 is required for proper heart development since knockdown of XWnt6 results in a non-beating heart and up-regulation of several of these myocardial markers. Complementary to this finding, activation of canonical Wnt signalling or over-expression of mouse Wnt6 inhibits mouse embryonic stem cell differentiation into beating cardiomyocytes. Wnt6 functions to restrict heart muscle differentiation. Due to Wnt6 expression within the pronephritic anlage and later within the pronephritic tubules, and because this kidney specific expression is conserved in mouse where Wnt6 is expressed in the ureter bud, we investigated an additional role for XWnt6 in kidney development. Knockdown of Wnt6 studies in <i>Xenopus</i> show that Wnt6 is clearly required for pronephros development since loss of XWnt6 function results in loss of expression of a number of pronephros-specific genes including many associated with MET such as Na<sup>+</sup> K<sup>+</sup>ATPase and NKCC2 which are required for proper tubule formation and function. Therefore, XWnt6 is not required for those genes that require XWnt4 expression and it appears instead that these two Wnt proteins work in parallel to direct expression of different genes required for kidney development. In addition, both gain and loss of XWnt6 function result in eye phenotype and XWnt6 function is required for expression of the proneural gene, Sox2. Furthermore, it appears likely that XWnt6 signals with the Wnt receptor Frizzzled5 to regulate expression of Sox2 in the developing retina to promote proper eye formation (Van Raay, Moore et al. 2005). In summary, XWnt6 restricts heart muscle differentiation whereas it is a positive regulator of kidney and eye development.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:439976 |
| Date | January 2006 |
| Creators | Heine, Danielle Lynn |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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