Molecular, Cell, Development (MCD) Seminar Series - McMaster University
2008-09 || 2009-10 || 2010-11 || 2011-12 || 2012-13

Molecular, Cell, Development (MCD) SEMINAR SERIES
Department of Biology


 
Speaker: Dr. Kristin Hope

Date: Friday 9th, November, 2012
Time: 12 noon
Location: HSC 1A5

Title: The potential redundant role(s) of AP-2alpha and AP-2beta in the neural retina

Abstract
Vertebrate eye development is an intricate process that requires appropriate tissue interactions and signalling beginning in early embryogenesis. A complex network of genes and transcription factors are crucial in facilitating proper changes in cell morphology, cell fate determination and cellular differentiation occurring during eye and lens. The Activating Protein-2 (AP-2) transcription factors are a family of genes playing essential roles in the development of multiple tissues, including the eye. There are five known AP-2 proteins encoded by separate genes (alpha to epsilon) that share evolutionarily conserved regions and similar structural and functional properties. Transgenic and knockout (KO) mouse models have revealed a major role for AP-2α in development of the lens, cornea, and more recently the neural retina and retinal pigmented epithelium. The West-Mays lab has shown that AP-2α and AP-2β have considerable overlap in expression in post-mitotic amacrine and horizontal cells of the retina. Since single mutants do not exhibit loss of these retinal cell types, our data supports the hypothesis that AP-2β and AP-2α functionally compensate for one another during retinogenesis. We have successfully created mutants with both AP-2α and AP-2β conditionally deleted from the developing retina. This seminar will describe the resulting defects observed in the developing horizontal and amacrine cells.

Recent evidence showing that mutations and/or deletions in the human AP-2α gene are linked to Brachio-oculo-facial syndrome (BOFS) resulting in multiple ocular defects. Those patients with mutations in AP-2α have more severe ocular defects than those with deletions, implying that mutations in AP-2α may cause a dominant negative effect that reduces the function of wild-type AP-2α and potentially other AP-2 family members. To investigate these specific mutations, we employed BOFS mouse mutants, in which the normal AP-2α allele was replaced by a mutant allele. Our examinations of these mouse embryos have begun to reveal some interesting ocular phenotypes, which will also be presented at this seminar.