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PhD Transfer Examination – Amanda Miles (Tropepe lab)

July 26, 2016 @ 10:10 am - 10:40 am

PhD Transfer Exam

 

Tuesday July 26th, 10:10 am – Ramsay Wright Building, Rm. RW 432

 

Amanda Miles (Tropepe lab)

Investigating the function of dmbx1 and znf644 through epigenetic interactions in the developing zebrafish retina

Abstract

The developing zebrafish retina initially consists entirely of proliferating retinal progenitor cells (RPCs), which are multipotent cells capable of differentiating into any of the 6 main retinal cell types. The transition from a RPC to post-mitotic, differentiated retinal cell requires RPCs exit the cell cycle, and repress the expression of progenitor and cell cycle genes, including vsx2 and cyclinD1, respectively.  However, we lack a detailed understanding of the molecular basis of how this transition is regulated.  Two genes implicated in controlling RPC cell cycle exit are the homeobox transcription factor, dmbx1 and the atypical zinc finger protein, znf644. Research in our lab has shown that knockdown of either gene results in a similar phenotype, showing prolonged RPC proliferation, concomitant reduction of retinal differentiation, and upregulated expression of vsx2 and cyclinD1. Evidence indicates that znf644 represses these genes by physically interacting with the histone methyltransferase, g9a, to deposit the repressive H3K9me2 on the gene promoters. However, whether dmbx1 interacts and functions together with this epigenetic machinery remains unknown. My preliminary data, through combinatorial gene knockdown of dmbx1 with znf644 or g9a supports a genetic interaction among these genes. Additionally, znf644 and dmbx1 knockdown similarly show a reduction of H3K9me2 marks in the retina indicating that loss of either gene impairs epigenetic gene silencing. I hypothesize that dmbx1, znf644 and g9a genetically and physically interact to form a repressive complex that silences RPC genes to promote cell exit. To test this hypothesis my objectives are aimed at (1) understanding whether dmbx1 and znf644 function cooperatively during retinal development (2) characterizing the chromatin modification during retinal development in wildtype and dmbx1/znf644 gene loss of function embryos and (3) identifying protein-protein interaction and direct transcriptional targets of dmbx1. This knowledge will provide insight into the molecular basis of retinal development and into the aetiology of retinal disorders, since human DMBX1 and ZNF644 have been linked to pathological retinal growth defects.

 

 

Ramsay Wright is a wheelchair accessible building.

 

 

Details

Date:
July 26, 2016
Time:
10:10 am - 10:40 am
Event Category:
Event Tags:

Venue

Ramsay Wright Building, Room 432
25 Harbord St.
Toronto, ON M5S 3G5 Canada