Interaction of the SHOX2 transcriptional regulator with the Sonic hedgehog signalling pathway in the developing mouse limb
Date
2019-12
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Abstract
The mouse Shox2 gene is a critical transcription factor for embryonic limb patterning. This work explored how Shox2 is regulated by employing the 4C technique, which allows one to identify DNA sites that frequently interact with a genomic region of interest. Our findings showed that many sites contact Shox2, indicating that its expression is controlled by a collection of enhancers. By using a transgenic reporter line, we found that the SHOX2 protein negatively regulates an enhancer of Shox2. To investigate the genetic relationship between Shox2 and the Sonic hedgehog pathway, we generated compound mutant mouse embryos and found that the characteristic proximal limb truncation in conditional Shox2 mutants was significantly rescued in the absence of functional Shh. Finally, we focused on identifying shared downstream targets of SHOX2 and Sonic hedgehog. Through whole mount in situ hybridization, we tracked changes in gene expression of candidate common target genes in mutant backgrounds.
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Keywords
development, mouse, limb, enhancer
Citation
Ljubojevic, A. (2019). Interaction of the SHOX2 transcriptional regulator with the Sonic hedgehog signalling pathway in the developing mouse limb (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.