Rbpj Direct Regulation of Atoh7 Transcription in the Embryonic Mouse Retina
Authors
Affiliations
In vertebrate retinal progenitor cells, the proneural factor Atoh7 exhibits a dynamic tissue and cellular expression pattern. Although the resulting Atoh7 retinal lineage contains all seven major cell types, only retinal ganglion cells require Atoh7 for proper differentiation. Such specificity necessitates complex regulation of Atoh7 transcription during retina development. The Notch signaling pathway is an evolutionarily conserved suppressor of proneural bHLH factor expression. Previous in vivo mouse genetic studies established the cell autonomous suppression of Atoh7 transcription by Notch1, Rbpj and Hes1. Here we identify four CSL binding sites within the Atoh7 proximal regulatory region and demonstrate Rbpj protein interaction at these sequences by in vitro electromobility shift, calorimetry and luciferase assays and, in vivo via colocalization and chromatin immunoprecipitation. We found that Rbpj simultaneously represses Atoh7 transcription using both Notch-dependent and -independent pathways.
Notch pathway mutants do not equivalently perturb mouse embryonic retinal development.
Bosze B, Suarez-Navarro J, Cajias I, Brzezinski Iv J, Brown N PLoS Genet. 2023; 19(9):e1010928.
PMID: 37751417 PMC: 10522021. DOI: 10.1371/journal.pgen.1010928.
Wong N, Yip S, Huang C Int J Mol Sci. 2023; 24(17).
PMID: 37686457 PMC: 10487913. DOI: 10.3390/ijms241713652.
Mapping of Notch signaling in the developing organ of Corti in common marmosets.
Hosoya M, Fujioka M, Okano H, Ozawa H Front Neuroanat. 2023; 17:1188886.
PMID: 37351521 PMC: 10282542. DOI: 10.3389/fnana.2023.1188886.
Ge Y, Chen X, Nan N, Bard J, Wu F, Yergeau D Nucleic Acids Res. 2023; 51(5):2151-2176.
PMID: 36715342 PMC: 10018358. DOI: 10.1093/nar/gkad026.
Luo Z, Chang K, Wu S, Sun C, Xia X, Nahmou M Stem Cell Reports. 2022; 17(12):2690-2703.
PMID: 36368332 PMC: 9768574. DOI: 10.1016/j.stemcr.2022.10.011.