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Title: Study of Nhlh2 transcription factor and its putative target genes in the retina
Author: Dellett, Margaret
ISNI:       0000 0001 3421 7484
Awarding Body: Queen's University of Belfast
Current Institution: Queen's University Belfast
Date of Award: 2008
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Chapter 1 provides an overview ofthe basIc helix-loop-helix (bHLH) and homeodomain families oftranscription factors (TFs) and their role in the developing retina, with examples of abnormal phenotypes associated with their targeted deletion or misexpression. The hypothesis ofNhlh2 involvement in retinogenesis is formulated and it will be tested in the following chapters. Chapter 2 describes the experimental methods employed. Chapter 3 reports Nhlh2 expression pattern by in situ hybridisation (ISH) and PCR in the developing and adult murine retina in the inner nuclear layer (INL) and ganglion cell layer (GCL). Expression of Nhlh2 was localised to amacrine and retinal ganglion cells (RGCs) in the postnatal retina and amacrine cells only in the adult retina by co-labelling experiments. Chapter 4 examines the retinal loss-of-function phenotype of the NhlhXI - and the Nhlhrl-NhlhXI - mouse through extensive immunohistochemical analysis of specific retinal cell types. No difference was detected in the number or location of amacrine cells and RGCs in the NhlIl2-1 - neonatal and adult retina. Preliminary data Logested the presence of aberrant phenotypes with variable penetrance in the GCL of Nhlhrl-NhlIlXI - retina. Chapter 5 explores the interaction between NIllll2 and other TFs in the developing retina. The neonatal NhlllXI . and Nhlhrl-NhlhXI - retina showed reduced expression of the TFs AP2-a, Barhl2, and ProxI whereas Foxn4 expression was up-regulated. Targeted deletion of Nhlll2 resulted in a mildly aberrant phenotype in· the GCL which became more evident upon deletion of both NlllhI and Nlllll2. Chapter 6 presents data from a microarray experiment, which detected changes in gene expression in the neonatal retina associated with Nhl1l2 targeted deletion. Some of the genes were further investigated by qRT-PCR and immunohistochemistry. Chapter 7 provides a general discussion, with concluding remarks for the main body of the thesis. The focus of this chapter is mainly suggestions for future work. Supplied by The British Library - 'The world's knowledge'
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available