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Roles of eBF Transcription Factors in Retinal Cell Type Specification

by
Kangxin Jin
MS, 2003
New Jersey Institute of Technology

Thesis Advisor: Mengqing Xiang, PhD
Graduate Program: Molecular Genetics, Microbiology & Immunology

CABM Conference Room 010
Busch Campus
Piscataway

Thursday, July 16, 2009
10:30 am


Abstract

The establishment of functional retinal circuits in the mammalian retina depends critically on the proper generation and assembly of six classes of neurons, five of them consist of two or many more subtypes that differ in morphologies, physiological properties and/or sublaminar positions. How these diverse neuronal types and subtypes arise during retinogenesis still remain largely to be defined at the molecular level. Here we show that all four family members of the Ebf helix-loop-helix (HLH) transcription factors are similarly expressed during retinogenesis in several neuronal types and subtypes and their precursors including ganglion, amacrine, bipolar and horizontal cells. Misexpressed Ebfs bias retinal precursors toward the fates of non-AII glycinergic amacrine, Type 2 OFF-cone bipolar and horizontal cells whereas a dominant-negative Ebf suppresses the differentiation of these cells as well as ganglion cells. Reducing Ebf1 expression by RNAi leads to an inhibitory effect similar to that of the dominant-negative Ebf, effectively neutralizes the promotive effect of wild-type Ebf1 but has no impact on the promotive effect of an RNAi-resistant Ebf1. These data indicate that Ebfs are both necessary and sufficient for specifying non-AII glycinergic amacrine, Type 2 OFF-cone bipolar and horizontal cells, whereas they are only necessary but not sufficient for specifying ganglion cells; and further suggest that Ebfs may cooperate with other retinogenic factors to ensure proper specification and differentiation of diverse retinal cell types and subtypes.


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