Activities and cooperation of Lef1 and Alx4 during mouse embryogenesis.
Published: 2006
Language: eng
Number of pages: 145
ISBN-13: 9780494160145
Description: The Wnt-signalling mediator, Lymphoid enhancer factor, Left1, regulates gene expression in response to Wnt signals and integrates a number of signalling cascades required for the development of embryonic and postnatal tissues. Lef1 facilitates the integration of multiple signal transduction pathways by virtue of its ability to complex factors and regulate transcription of target genes. Specifically in this thesis, I have identified a novel molecular and genetic interaction with the paired-like homeodomain protein, Aristaless-like 4, Alx4. This thesis demonstrates that through their coordinate activities, these proteins cooperate in the transcriptional regulation of target genes and subsequent development of the mouse embryo. I have established that Alx4 interacts with Lef1 and that these transcription factors synergize in the regulation of the NCAM promoter. Furthermore, Lef1 transcriptional activity can be regulated by Alx4 in a dose-dependent manner. This molecular interaction is supported by subsequent genetic studies in mice where loss of function of both of these transcription factors results in early embryonic lethality. Finally, I examined the role of Left1 during embryonic mammary gland development. I demonstrated that mesenchymal-epithelial Wnt-signalling is required during embryonic mammary gland development in the absence of Lef1. These studies provide novel insight into potential mechanisms by which Lef1 activities can regulate and be regulated by different pathways during normal embryonic development and cancer.
Notes: Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3564.

Thesis (Ph.D.)--University of Toronto, 2006.

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