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Transcriptional regulation of the platelet-derived growth factor alpha receptor (PDGFRA) gene during development

Flores-Garcia, Lisbeth; (2007) Transcriptional regulation of the platelet-derived growth factor alpha receptor (PDGFRA) gene during development. Doctoral thesis , UCL (University College London). Green open access

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Abstract

The platelet-derived growth factor receptor (alpha subunit, pdgfra) is essential for the development of several types of precursor cells and their differentiated progeny for example, the cranial neural crest cells (CNCC), mesenchyme derived-cells (MSdC) and oligodendrocyte progenitors (OLPs) in the central nervous system. Previous studies suggested that separate c/s-acting specific regulatory elements (SREs) are required to drive pdgfra expression in different types of progenitor cells during development. As a first step towards understanding the control of pdgfra transcriptional regulation I set out to identify and characterize SREs in vivo. I analyzed 16 human PDGFRA-YAC/BAC mice transgenic lines, most of which I generated myself, and compared their PDGFRA expression patterns with each other and with previously-generated PDGFRA transgenics during development. These new transgenes gave me a better understanding of PDGFRA transcriptional regulation and allowed me to further refine the locations of many important SREs of this gene. Most of the SREs controlling expression in CNCC, sclerotome progenitors, MSdC, and first and second branchial arches seem to be located in the 3 kb upstream sequence of the PDGFRA gene. In addition, the postnatal OLP (pOLP)-SREs appear to lie in a region up to 63 kb downstream of the coding sequence. Furthermore, I used bioinformatic analysis to search for evolutionarily conserved sequences (CS) in the non-coding genomic sequence of the human PDGFRA gene, and found that the 3'-untranslated region has CSs, some of which might be pOLP-SREs because they are present in chicken, Xenopus and mammals but not zebrafish, in keeping with the observation that OLPs in all tetrapods examined - but not fish - express pdgfra in their OLPs. Overall, my results suggest a 'temporal colinearity' model of SREs for transcriptional activation of the pdgfra gene during development and that its expression might be managed by separate embryonic and postnatal regulatory systems.

Type: Thesis (Doctoral)
Title: Transcriptional regulation of the platelet-derived growth factor alpha receptor (PDGFRA) gene during development
Identifier: PQ ETD:593650
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest. Third party copyright material has been removed from the ethesis. Images identifying individuals have been redacted or partially redacted to protect their identity.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/1446305
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