Investigating the role of the Shox2 gene desert in mouse limb and brain development
Date
2024-02-14
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Abstract
A major challenge in biology is determining what governs the precise spatiotemporal gene expression required to pattern the vertebrate embryo. As vertebrate genomes continue to be sequenced, the presence of large, noncoding regions of DNA termed gene deserts are found with prominence. Complete with the information that they are often highly conserved and located near important developmental genes (such as the short stature homeobox 2 gene; Shox2), gene deserts have become a focus for their potential in cis-regulatory governance. The work in this thesis partially uncovers the regulatory mechanism of Shox2; a gene with pleiotropic developmental functions in mice located upstream of a 675 kb gene desert (S2GD) with cis-regulatory sequences that have activity in the limb and brain of transgenic mice. Our findings show that Shox2 expression in the mouse limb and brain partially requires the presence of the S2GD. More specifically, following a removal of the majority of the S2GD (582 kb) and a sensitized genetic background for Shox2 in the limb (whereby all Shox2 expression in the limb comes from the allele lacking the majority of the S2GD), mice display abnormal proximal limb formation that proceeds into adulthood. Second, when mice are bred on a sensitized genetic background for Shox2 in the central nervous system (CNS) (this time with all Shox2 expression in the CNS coming from the allele lacking the majority of the S2GD), mice not only display aberrant exploratory behaviour and motor coordination in both sexes, but reduced Shox2 expression in E12.5 hindbrain nuclei (n=3) and an overexpression of Shox2 in P1 pontine nuclei (n=2). Ultimately, the work in this thesis provides a paradigm for the regulation of an important developmental gene in mice, brought forth in part by the downstream gene desert.
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Shox2, limb development, brain development, developmental biology, biology, neuroscience, gene desert, mice, mouse, mus musculus
Citation
Festa-Daroux, T. A. (2024). Investigating the role of the Shox2 gene desert in mouse limb and brain development (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.