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Publication : Pou3f1 orchestrates a gene regulatory network controlling contralateral retinogeniculate projections.

First Author  Fries M Year  2023
Journal  Cell Rep Volume  42
Issue  8 Pages  112985
PubMed ID  37590135 Mgi Jnum  J:339296
Mgi Id  MGI:7521880 Doi  10.1016/j.celrep.2023.112985
Citation  Fries M, et al. (2023) Pou3f1 orchestrates a gene regulatory network controlling contralateral retinogeniculate projections. Cell Rep 42(8):112985
abstractText  The balance of contralateral and ipsilateral retinogeniculate projections is critical for binocular vision, but the transcriptional programs regulating this process remain ill defined. Here we show that the Pou class homeobox protein POU3F1 is expressed in nascent mouse contralateral retinal ganglion cells (cRGCs) but not ipsilateral RGCs (iRGCs). Upon Pou3f1 inactivation, the proportion of cRGCs is reduced in favor of iRGCs, leading to abnormal projection ratios at the optic chiasm. Conversely, misexpression of Pou3f1 in progenitors increases the production of cRGCs. Using CUT&RUN and RNA sequencing in gain- and loss-of-function assays, we demonstrate that POU3F1 regulates expression of several key members of the cRGC gene regulatory network. Finally, we report that POU3F1 is sufficient to induce RGC-like cell production, even in late-stage retinal progenitors of Atoh7 knockout mice. This work uncovers POU3F1 as a regulator of the cRGC transcriptional program, opening possibilities for optic nerve regenerative therapies.
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