Open AccessARS2 is required for retinal progenitor cell S-phase progression and Müller glial cell fate specification
Author(s) -
Connor O’Sullivan,
Philip E.B. Nickerson,
Oliver A. Krupke,
Jennifer Christie,
Lili Chen,
Monica Mesa-Peres,
Minyan Zhu,
Bridget C. Ryan,
Robert L. Chow,
Perry L. Howard
Publication year - 2020
Publication title -
biochemistry and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.843
H-Index - 91
eISSN - 1208-6002
pISSN - 0829-8211
DOI - 10.1139/bcb-2018-0250
Subject(s) - retinal , progenitor cell , progenitor , cell , retina , biology , microbiology and biotechnology , muller glia , cell fate determination , neuroscience , stem cell , genetics , biochemistry , gene , transcription factor
During a developmental period that extends postnatally in the mouse, proliferating multipotent retinal progenitor cells produce one of 7 major cell types (rod, cone, bipolar, horizontal, amacrine, ganglion, and Müller glial cells) as they exit the cell cycle in consecutive waves. Cell production in the retina is tightly regulated by intrinsic, extrinsic, spatial, and temporal cues, and is coupled to the timing of cell cycle exit. Arsenic-resistance protein 2 (ARS2, also known as SRRT) is a component of the nuclear cap-binding complex involved in RNA Polymerase II transcription, and is required for cell cycle progression. We show that postnatal retinal progenitor cells (RPCs) require ARS2 for proper progression through S phase, and ARS2 disruption leads to early exit from the cell cycle. Furthermore, we observe an increase in the proportion of cells expressing a rod photoreceptor marker, and a loss of Müller glia marker expression, indicating a role for ARS2 in regulating cell fate specification or differentiation. Knockdown of Flice Associated Huge protein (FLASH), which interacts with ARS2 and is required for cell cycle progression and 3′-end processing of replication-dependent histone transcripts, phenocopies ARS2 knockdown. These data implicate ARS2–FLASH-mediated histone mRNA processing in regulating RPC cell cycle kinetics and neuroglial cell fate specification during postnatal retinal development.