Control of Cardiac and Limb Development by the bHLH Transcription Factors DHAND and eHAND

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Title: Control of Cardiac and Limb Development by the bHLH Transcription Factors DHAND and eHAND
Author: McFadden, David Glenn
Abstract: Members of the basic helix -loop -helix (bHLH ) transcription factor family regulate the specification and differentiation of multiple cell lineages during embryonic development . The bHLH proteins dHAND and eHAND are expressed in complimentary and overlapping patterns during embryogenesis , and gene knockout studies have demonstrated that dHAND and eHAND null embryos die from defects in right ventricular and placental development , respectively . Therefore , we have investigated three aspects of HAND gene biology . Firstly , in order to determine the mechanisms that establish chamber identity during cardiac development , we have identified a transcriptional enhancer that controls dHAND expression in the embryonic right ventricle , and demonstrated that activity of this element depends on paired binding sites for the GATA family of zinc -finger transcription factors . Secondly , we have generated floxed alleles of murine eHAND in order to investigate the role of eHAND during heart formation . These studies have identified a novel role for eHAND during cardiac valve formation , and demonstrated genetic redundancy of HAND genes during mammalian cardiac morhpogenesis . Finally , we have utilized tissue culture assays and transgenic mice to investigate the mechanisms by which dHAND regulates transcription of downstream target genes . These results suggest that dHAND and eHAND may regulate gene expression independently of direct DNA binding and transcriptional activation .
URI: http : / /hdl .handle .net /2152 .5 /785
Date: 2004-05-04

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Control of Cardiac and Limb Development by the bHLH Transcription Factors DHAND and eHAND. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /785 .

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