Investigating the role of the Shox2 gene desert in mouse limb and brain development

Festa-Daroux, Tabitha Anne

Investigating the role of the Shox2 gene desert in mouse limb and brain development

dc.contributor.advisor	Cobb, John Andrew
dc.contributor.author	Festa-Daroux, Tabitha Anne
dc.contributor.committeemember	Summers, Mindi
dc.contributor.committeemember	Chua, Gordon
dc.contributor.committeemember	Dyck, Richard Henry
dc.date	2024-06
dc.date.accessioned	2024-02-29T18:45:03Z
dc.date.available	2024-02-29T18:45:03Z
dc.date.issued	2024-02-14
dc.description.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.
dc.identifier.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.
dc.identifier.uri	https://hdl.handle.net/1880/118234
dc.language.iso	en
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject	Shox2
dc.subject	limb development
dc.subject	brain development
dc.subject	developmental biology
dc.subject	biology
dc.subject	neuroscience
dc.subject	gene desert
dc.subject	mice
dc.subject	mouse
dc.subject	mus musculus
dc.subject.classification	Biology
dc.subject.classification	Biology--Molecular
dc.subject.classification	Neuroscience
dc.title	Investigating the role of the Shox2 gene desert in mouse limb and brain development
dc.type	master thesis
thesis.degree.discipline	Biological Sciences
thesis.degree.grantor	University of Calgary
thesis.degree.name	Master of Science (MSc)
ucalgary.thesis.accesssetbystudent	I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.