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Learn MoreDifferentiation of distinct neurons in the developing retina is controlled by combinatorial action of a small subset of transcription factors and signalling molecules. Protein inhibitor of activated STAT3 (PIAS3) has been implicated in guiding the specification of both rod and cone photoreceptors through posttranslational modification of key retinal transcription factors. To investigate its role during retinal development, we deleted exon 2-5 of the mouse Pias3 gene, which resulted in complete loss of the PIAS3 protein. Pias3-/- mice did not exhibit any overt phenotype, and retinal lamination appeared normal by histology even at 18 months. We detected reduced photopic b-wave amplitude by electroretinography (ERG) analysis following green light stimulation of Pias3-/- retina at postnatal day (P) 21, suggesting a compromised visual response of medium wavelength (M) cones. No change was evident in response of short wavelength (S) cones or rod photoreceptors until 7 months. Immunohistochemistry demonstrated altered distribution of cone photoreceptors as revealed by increased S-opsin expression in the M-cone dominant dorsal retina. Transcriptome profiling of P21 and 18-month old Pias3-/- retina revealed aberrant expression of genes associated with photoreceptor function. Our studies suggest redundancy in SUMOylation-associated transcriptional control mechanisms and identify a specific though limited role of PIAS3 in modulating spatial patterning and optimal function of cone photoreceptor subtypes in the mouse retina. SOURCE: Jerome,Eric,Roger (jeromeeroger@gmail.com) - Neuro-PSI CNRS-Universite Paris Sud
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