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Xiangmei Zhang, Takao Hasimoto, Xian-Jie Yang; Characterization of the Neurogenic Potential of Human ATOH7 in the Developing Chicken Retina. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1767.
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© ARVO (1962-2015); The Authors (2016-present)
In order to determine the neurogenic potentials of the human bHLH transcription factor ATOH7, especially its ability to influence retinal ganglion cell (RGC) development during early retinogenesis.
Human ATOH7 cDNA was cloned into the avian replication incompetent retroviral vector RCAS.The RCAS.ATOH7 viral stock was used to infect chicken embryonic eyes prior to the onset of retinogenesis and during the peak period of chicken RGC genesis. The RCAS virus encoding eGFP was used as a control. Infected chicken retinas were harvested and analyzed at various developmental stages to assess the production of RGCs using immunocytochemistry and FACS analyses. The influence of forced ATOH7 expression on cell cycle progression was analyzed using BrdU pulse-labeling and FACS quantification.
Precocious expression of ATOH7 in the pre-neurogenic retina results in sparse induction of RGC formation in the peripheral retina. Not all infected progenitors exist the cell cycle and become RGCs. Among the ectopic RGCs, their nascent axons are often wondering and misprojected. In the neurogenic retina, viral mediated ATOH7 expression significantly enhances RGC production, with thickened RGC fiber layer and axon bundles. Cell cycle analyses indicate that viral driven ATOH7 expression resulted in accelerated progression from the G2 to M2 phase, and cell cycle exit. Despite the overproduction of RGC during the peak period of RGC genesis, an increased RGC death occurred during the period of retinotectal connection.
Human neurogenic factor ATOH7 can significantly enhance RGC production from a neurogenic retinal epithelium, but is less cable to induce precocious neurogenesis, suggesting that other factors and conditions may also dictate RGC development. Elevated cellular ATOH7 levels lead to shortened G2/M transition, leading to cell cycle exit. Persistent ATOH7 expression in postmitotic RGCs is likely detrimental to cell survival. These results have implication to stem cell based strategies to produce retinal neurons from differentiated optic vesicles.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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