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http://theses.ncl.ac.uk/jspui/handle/10443/3668
Title: | Msx1 modulates the Pax9-null cardiovascular phenotype |
Authors: | Khasawneh, Ramada Rateb Abdel Karim |
Issue Date: | 2017 |
Publisher: | Newcastle University |
Abstract: | Development of the aortic arch arteries from the pharyngeal arch arteries is a complex process requiring the interaction of several tissue types and tightly regulated gene expression during embryogenesis. In this work, the role of transcription factor Pax9 in cardiovascular development was investigated using transgenic mice, imaging techniques and gene expression analysis. Pax9 is specifically expressed in the pharyngeal endoderm at mid-embryogenesis, and Pax9-null mice die at birth from defects in the formation and remodeling of the 3rd and 4th pharyngeal arch arteries resulting in absent common carotid arteries, aberrant right subclavian artery and interrupted aortic arch. The aim of the work presented in this thesis was to identify genes that potentially acting in the same genetic regulatory network as Pax9 to control cardiovascular development. The transcription factor Msx1 was selected as this was shown to interact with Pax9 in tooth development, and transgenic mice lacking Msx1 and Msx2 display cardiovascular defects. Surprisingly, this analysis shows that mice simultaneously null for Pax9 and heterozygous for Msx1 have a significantly reduced incidence of aortic arch defects compared to Pax9 –/– mice. Although Pax9 and Msx1 proteins can interact during tooth formation, the expression of these two genes does not overlap in the pharyngeal arches, with Msx1 being expressed in neural crest cells. Immunohistochemistry labelling revealed that more neural crest cells were present within the 3rd pharyngeal arch of Pax9 –/–;Msx1+/– embryos compared to Pax9 –/– embryos, which suggesting a role for these cells in protecting the 3rd pharyngeal arch artery from regressing as observed in Pax9 –/– embryos. In addition, a thick layer of smooth muscle around the 3rd PAA in Pax9 –/–;Msx1+/– embryos compared to Pax9 –/– embryos was observed, , all together indicating that neural crest cells differentiate to smooth muscle in Pax9 –/–;Msx1+/– embryos and this help protect and support the 3rd PAA during remodeling. Our data therefore show that Msx1 heterozygosity appears to modulate the Pax9-null cardiovascular phenotype by a yet unrecognized mechanism. |
Description: | PhD Thesis |
URI: | http://hdl.handle.net/10443/3668 |
Appears in Collections: | Institute of Genetic Medicine |
Files in This Item:
File | Description | Size | Format | |
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Khasawneh, R.K. 2017.pdf | Thesis | 12.52 MB | Adobe PDF | View/Open |
dspacelicence.pdf | Licence | 43.82 kB | Adobe PDF | View/Open |
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