Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.683382
Title: The relationship between the transcription factors Prdm8 and Bhlhb4 in the development of the retina and central nervous system
Author: Woods, Sasha Marie
ISNI:       0000 0004 5916 2442
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2014
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Abstract:
Elucidating the relationship between transcription factors responsible for regulating the complex genetic network that drives ocular development enhances our understanding of this network and allows us to identify defects that may underlie causes of human blindness. Furthermore, many transcription factors crucial in eye development are also essential in brain development; thus an understanding of these genetic networks also allows us to understand the aetiology of some neuroanatomical and neurobehavioural CNS deficits. PRDM8 and BHLHB4 are two transcription factors expressed in retina and CNS. Strikingly, adult Prdm8eGFP/eGFP and Bhlhb4-/- mice have overlapping retinal phenotypes, with both mutants showing a loss of rod bipolar cells. Rod bipolar cell loss causes a visual deficit in scotopic conditions, and both Prdm8eGFP/eGFP and Bhlhb4-/- mice demonstrate b-wave deficits on dark-adapted Electroretinograms. This deficit mimics the human disorder Congenital Stationary Night Blindness. PRDM8 acts in a transcriptional complex with BHLHB5 to regulate gene expression in the developing CNS and Prdm8eGFP/eGFP and Bhlhb5-/- mice have overlapping phenotypes. As BHLHB4 is highly homologous to BHLHB5, I hypothesised that PRDM8 might have a similar genetic relationship with BHLHB4 in the development of rod bipolar cells and that loss of PRDM8 or BHLHB4 function might lead to overlapping neuroanatomical and neurobehavioural CNS deficits. I have found that Prdm8 and Bhlhb4 act in parallel genetic pathways to regulate the development of rod bipolar cells and are unlikely to have a genetic relationship in the hippocampus. Despite being co-expressed in developing rod bipolar cells, PRDM8 and BHLHB4 do not regulate overlapping sets of genes, indicating that they do not act in a common genetic pathway. In the hippocampus, PRDM8 and BHLHB4 are co-expressed in neuronal populations. However, whilst Prdm8eGFPl eGFP mice have cellular hippocampal defects as well as deficits in tests of spatial learning and memory, Bhlhb4-/- mice have no neurobehavioural abnormalities or cellular defects of the hippocampus.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.683382  DOI: Not available
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