Weber, SJM;
(2016)
Id4: an inhibitory function in the control of hair cell formation?
Masters thesis (PhD), UCL (University College London).
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Abstract
Mechanosensitive hair cells in the sensory epithelia of the vertebrate inner ear are essential for hearing and the sense of balance. Initially formed during embryological development they are constantly replaced in the adult avian inner ear after hair cell damage and loss, while practically no spontaneous regeneration occurs in mammals. The detailed molecular mechanisms that regulate hair cell formation remain elusive despite the identification of a number of signalling pathways and transcription factors involved in this process. In this study I investigated the role of Inhibitor of differentiation 4 (Id4), a member of the inhibitory class V of bHLH transcription factors, in hair cell formation. I found that Id4 is expressed in both hair cells and supporting cells of the chicken and the mouse inner ear at stages that are crucial for hair cell formation. In addition, forced overexpression of Id4 appeared to inhibit hair cell formation in the developing chicken inner ear while deletion of the Id4 gene did not result in an obvious phenotype in mice. When looking at Id4 gene regulation, luciferase reporter experiments revealed that Id4 expression is driven by Notch activity; however, blockade of this pathway did not reduce the levels of Id4 and it seems likely that Id4 expression is regulated by different pathways and mechanisms at a time. Together, these results indicate that Id4 could regulate hair cell formation during embryological development; however its exact function remains unclear. The fact that Id4 expression was also found in differentiated hair cells is inconsistent with the hypothesis of Id4 merely blocking hair cell formation. It seems likely that the function of Id4 is rather determined by expression levels and the presence or absence of interacting bHLH partners. Thus, a detailed analysis of levels of expression in a tissue- and developmental stagespecific manner as well as consideration of other expressed bHLH transcription factors are required for a deeper understanding of the complex transcriptional network that regulates hair cell formation.
| Type: | Thesis (Masters) |
|---|---|
| Qualification: | PhD |
| Title: | Id4: an inhibitory function in the control of hair cell formation? |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1476313 |
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