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Xiaohuan Xia, Sowmya Parameswaran, Iqbal Ahmad; INFLUENCE OF HMGA2 ON PHOTORECEPTOR DIFFERENTIATION. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3982.
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The high-mobility group AT-hook 2 (Hmga2) protein regulates transcription by modulating the chromatin structure. Hmga2 and its microRNA regulator Let7 are expressed in a reciprocal manner in the developing retina; levels of Hmga2 transcripts temporally decreases and Let7 microRNA increases with the exhaustion of retinal progenitors as differentiation comes to an end. Hmga2 is expressed in retinal progenitors and we demonstrated earlier that it regulates the self-renewal of retinal progenitors (Parameswaran et al., 2013, ARVO Abst). Here, we have examined whether or not Hmga2 expression or the lack of it has any influence on the differentiation potential of retinal progenitors during late retinal histogenesis.
We carried out Hmga2 gain-of-function (GOF) and loss-of-function (LOF) experiments using lentivirus-mediated perturbation of expression in E18 retinal progenitor and E18 retinal explant models of retinal differentiation. The perturbation of Hmga2 expression was verified by Q- PCR and immunofluorescence analyses. The effects of the perturbations on the differentiation of the late born cells, i.e., rod photoreceptors, bipolar cells, and Müller glia were ascertained by examining the expression of regulators and markers of the specific cell types using analyses mentioned above.
We observed that both in retinal progenitor and retinal explant models, levels of Hmga2 expression were decreased with differentiation. When Hmga2 expression was maintained by Hmga2 lentivirus-mediated transduction, differentiation of rod photoreceptors was negatively impacted, compared to controls. In contrast, when Hmga2 expression was prematurely decreased by Hmga2 siRNA lentivirus-mediated transduction a significantly higher number of rod photoreceptors were observed, compared to controls. In both GOF and LOF experiments, no significant difference in the number of either bipolar cells or Müller glia was observed.
Our preliminary results suggest that Hmga2, which is an intrinsic regulator of self-renewal of retinal progenitors, extends its influence on rod photoreceptor differentiation.
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