June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Pou4f1-mediated regulatory network in the development of retinal ganglion cells
Author Affiliations & Notes
  • Takae Kiyama
    Ophthalmology and Visual Science, The University of Texas Health Science Center at Houston, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Takae Kiyama None
  • Footnotes
    Support  NIH grant EY024376
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1349 – F0280. doi:
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    • Get Citation

      Takae Kiyama; Pou4f1-mediated regulatory network in the development of retinal ganglion cells. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1349 – F0280.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : POU family transcription factors play pivotal roles in the development of retinal ganglion cells (RGCs). Pou4f1 is a member of the family and is expressed in the newly differentiated RGCs. Although its roles in RGC differentiation and dendritic morphogenesis have been described, it is unclear how Pou4f1 regulates downstream effector genes to promote newly differentiated RGCs into functional RGC subtypes.

Methods : To identify genes regulated directly by Pou4f1, we conducted CUT&TAG sequencing using an anti-Pou4f1 antibody and developing mouse retinas. We performed immunostaining and in situ hybridization on control and Pou4f1-deleted retinas to validate potential targets.

Results : CUT&TAG sequencing revealed ~8000 Pou4f1 binding regions in developing mouse retinas. Many of these Pou4f1-bound regions are located in genes that encode transcription factors, and some of these TFs are known to play a role in retinal development and RGC subtype formation. Additionally, many genes involved in axon guidance and nervous system development are also direct targets of Pou4f1. We have validated some of these candidate targets in control and Pou4f1-deleted retinas. We are currently exploring whether some of these Pou4f1-bound regions can serve as RGC subtype-specific enhancers.

Conclusions : We have revealed a Pou4f1-mediated regulatory network in RGC development through direct and indirect modes. Pou4f1 directly regulates genes involving in axon guidance and neuronal development. Indirectly, Pou4f1 may control transcription factors functioning in RGC subtype specification and differentiation. We have also uncovered the self-regulation of Pou4f1, confirming a previous study. Furthermore, we discovered that Pou4f1 binds to the promoters of several upstream regulators, including Atoh7, Pou4f2 and Isl1, implicating potential feedback regulatory loops between Pou4f1 and these key RGC regulators in RGC formation.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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