title: Combinatorial regulation of optic cup progenitor cell fate by SOX2 and PAX6.
abstract: In humans, haploinsufficiency of either SOX2 or PAX6 is associated with microphthalmia, anophthalmia or aniridia. In this study, through the genetic spatiotemporal specific ablation of SOX2 on both wild-type and Pax6-haploinsufficent backgrounds in the mouse, we have uncovered a transcriptionally distinct and developmentally transient stage of eye development. We show that genetic ablation of SOX2 in the optic cup results in complete loss of neural competence and eventual cell fate conversion to non-neurogenic ciliary epithelium. This cell fate conversion is associated with a striking increase in PAX6, and genetically ablating SOX2 on a Pax6-haploinsufficient background partially rescues the Sox2-mutant phenotype. Collectively, these results demonstrate that precise regulation of the ratio of SOX2 to PAX6 is necessary to ensure accurate progenitor cell specification, and place SOX2 as a decisive factor of neural competence in the retina.
authors.affiliation: UNC Neuroscience Center, University of North Carolina at Chapel Hill, NC 27599, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Matsushima
authors.forename: Whitney
authors.initials: W
authors.lastname: Heavner
authors.forename: Larysa H
authors.initials: LH
authors.lastname: Pevny
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002924:Ciliary Body / Q000166:cytology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse