RRC ID 19261
Author Lin YP, Ouchi Y, Satoh S, Watanabe S.
Title Sox2 plays a role in the induction of amacrine and Müller glial cells in mouse retinal progenitor cells.
Journal Invest Ophthalmol Vis Sci
Abstract PURPOSE:The transcription factor Sox2 plays important roles in both human and mouse retinal development. Although loss-of-function mutations in Sox2 have been studied in mice, gain-of-function experiments in the neural retina have been lacking.
METHODS:The detailed expression pattern of Sox2 in the developing mouse retina was examined by immunohistochemistry. Then, Sox2 was expressed in a retinal explant culture prepared from E17 mouse embryos by retrovirus-mediated gene transfer to examine its role in retinal development. In addition, shRNA was used to suppress Sox2 in a retinal explant using a retrovirus-mediated system.
RESULTS:Sox2 was expressed throughout the neuroblastic layer in the embryonic retina, but only in the inner nuclear layer in the mature retina. Double immunostaining revealed that Sox2 was expressed in Müller glial cells and in a subset of amacrine cells. Forced expression of Sox2 in a mouse retinal explant culture resulted in the dramatic accumulation of amacrine cells in the inner nuclear layer; in addition, cells expressing amacrine cell markers were also found on the innermost side of the outer nuclear layer. The expression of Pax6, which plays an important role in amacrine cell differentiation, was observed in the Sox2-expressing cells, and Sox2 activated the Pax6 promoter to drive luciferase expression in Y79 cells. A decrease in retinal progenitor cell proliferation accompanied these effects. The suppression of Sox2 expression by shRNA resulted in a decreased number of cells in the inner nuclear layer.
CONCLUSIONS:Therefore, ectopic Sox2 expression can induce amacrine cells in the mouse retina from stage E17 onward, possibly by facilitating cell cycle exit.
Volume 50(1)
Pages 68-74
Published 2009-1-1
DOI 10.1167/iovs.07-1619
PII iovs.07-1619
PMID 18719084
MeSH Amacrine Cells / metabolism* Animals Cell Differentiation / physiology Cell Proliferation Cells, Cultured DNA Primers / chemistry Eye Proteins / genetics Fluorescent Antibody Technique, Indirect Gene Expression Regulation, Developmental / physiology* Gene Transfer Techniques Homeodomain Proteins / genetics Mice Mice, Inbred ICR Neuroglia / metabolism* PAX6 Transcription Factor Paired Box Transcription Factors / genetics Plasmids RNA, Messenger / metabolism Repressor Proteins / genetics Retina / embryology* Retroviridae / genetics Reverse Transcriptase Polymerase Chain Reaction SOXB1 Transcription Factors / genetics* Stem Cells / cytology* Transcriptional Activation
IF 3.47
Times Cited 49
Human and Animal Cells Y79(RCB1645)