Purchase this article with an account.
Zbynek Kozmik, Naoko Fujimura, Barbora Antosova; The role of Meis genes in retina development.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3115.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
While significant insights into the functional role of some transcription factors for eye formation have been accomplished, much less is known about the intricate wiring of the gene regulatory network (GRN) that controls the earliest stages of eye development. Here we focus on the role of Meis homeobox genes in mammalian retina development.
Using conditional gene targeting in mice at optic cup stage we provide evidence of a role of Meis genes in the process of retina development. We performed differential transcriptomics analysis at embryonic day E12.5 and E14.5 using wild type and Meis-deficient retinae in order to identify genes directly or indirectly regulated by Meis transcription factors. Quantitative RT-PCR was used to validate differential gene regulation in retina of wild type and Meis-deficient mice. Chromatin immunoprecipitation (ChIP) using anti-Meis antibody was performed on evolutionarily conserved non-coding regions of selected genes identified in differential transcriptomics screen.
We demonstrate that Meis-deficient retinae are hypocellular, and that expression of genes involved in cell-cycle regulation, such as cyclin D1 and cyclin D2, is affected. In addition, we found that differentiation of early-born cell types is aberrant in Meis-deficient retinae. By combining the transcriptomic and ChIP data we identified the 450bp-long alpha-enhancer, located in the third intron of the Pax6 gene, as a direct target of Meis transcription factors.
Combined, our data indicate that Meis homeoproteins are key regulators of retina cell proliferation and differentiation.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only