title: The proliferation and expansion of retinal stem cells require functional Pax6.
abstract: Retinal stem cells (RSCs) exist as rare pigmented ciliary epithelial cells in adult mammalian eyes. We hypothesized that RSCs are at the top of the retinal cell lineage. Thus, genes expressed early in embryonic development to establish the retinal field in forebrain neuroectoderm may play important roles in RSCs. Pax6, a paired domain and homeodomain-containing transcription factor, is one of the earliest genes expressed in the eye field and is considered a master control gene for retinal and eye development. Here, we demonstrate that Pax6 is enriched in RSCs. Inactivation of Pax6 in vivo results in loss of competent RSCs as assayed by the failure to form clonal RSC spheres from the optic vesicles of conventional Pax6 knockout embryos and from the ciliary epithelial cells of adult Pax6 conditional knockout mice. In vitro clonal inactivation of Pax6 in adult RSCs results in a serious proliferation defect, suggesting that Pax6 is required for the proliferation and expansion of RSCs.
authors.affiliation: Department of Medical Genetics and Microbiology, University of Toronto, and Program in Developmental Biology and Genetics, Research Institute, Hospital for Sick Children, Canada. shunbin_xu@rush.edu
authors.forename: Shunbin
authors.initials: S
authors.lastname: Xu
authors.forename: Mary E
authors.initials: ME
authors.lastname: Sunderland
authors.forename: Brenda L K
authors.initials: BL
authors.lastname: Coles
authors.forename: Angela
authors.initials: A
authors.lastname: Kam
authors.forename: Tamara
authors.initials: T
authors.lastname: Holowacz
authors.forename: Ruth
authors.initials: R
authors.lastname: Ashery-Padan
authors.forename: Till
authors.initials: T
authors.lastname: Marquardt
authors.forename: Roderick R
authors.initials: RR
authors.lastname: McInnes
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins