Coordinating progenitor cell cycle exit and differentiation in the developing vertebrate retina.
The proper development of the vertebrate retina relies heavily on producing the correct number and type of differentiated retinal cell types. To achieve this, proliferating retinal progenitor cells (RPCs) must exit the cell cycle at an appropriate time and correctly express a subset of differentiation markers that help specify retinal cell fate. Homeobox genes, which encode a family of transcription factors, have been accredited to both these processes, implicated in the transcriptional regulation of important cell cycle components, such as cyclins and cyclin-dependent kinases, and proneural genes. This dual regulation of homeobox genes allows these factors to help co-ordinate the transition from the proliferating RPC to postmitotic, differentiated cell. However, understanding the exact molecular targets of these factors remains a challenging task. This commentary highlights the current knowledge we have about how these factors regulate cell cycle progression and differentiation, with particular emphasis on a recent discovery from our lab demonstrating an antagonistic relationship between Vsx2 and Dmbx1 to control RPC proliferation. Future studies should aim to further understand the direct transcriptional targets of these genes, additional co-factors/interacting proteins and the possible recruitment of epigenetic machinery by these homeobox genes.
Department of Cell & Systems Biology, University of Toronto , Toronto, Ontario, Canada.
Amanda
A
Miles
Department of Cell & Systems Biology, University of Toronto, Toronto, Ontario, Canada; Department of Ophthalmology & Vision Sciences; Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Ontario, Canada.
Vincent
V
Tropepe
cell cycle; development; dmbx1; epigenetic; gene expression; mouse; neurogenesis; progenitor cell; retina; vsx2; zebrafish