title: Transcription factors SOX4 and SOX11 function redundantly to regulate the development of mouse retinal ganglion cells.
abstract: SOX family proteins belong to the high-mobility-group (HMG) domain-containing transcription factors, and function as key players to regulate embryonic development and cell fate determination. The highly related group C Sox genes Sox4 and Sox11 are widely expressed in the development of mouse retina and share a similar expression pattern with each other in this process. Here, to investigate the roles of Sox4 and Sox11 in the retinal development, Sox4, Sox11, and Sox4/Sox11 conditional knock-out (CKO) mice with deletion of Sox4, Sox11, and Sox4/Sox11 in retinas were generated. Our studies demonstrated that targeted disruption of Sox4 or Sox11 in retinas caused a moderate reduction of generation of RGCs. However, a complete loss of RGCs was observed in Sox4/Sox11-null retinas, suggesting the two genes play similar roles in the development of RGCs. Our further analysis confirms that Sox4 and Sox11 function redundantly to regulate the generation of RGCs at early embryonic stages as well as the survival of RGCs at late embryonic stages. In addition, we demonstrated that loss of Math5 impairs the expression of Sox4 and Sox11 in the ganglion cell layer while deletion of Brn3b has no effect on the expression of Sox4 and Sox11. Taken together, these findings elucidate SoxC genes as essential contributors to maintain the survival of RGCs, and imply their intermediate position between Math5 and Brn3b in the genetic hierarchy of RGC development.
authors: Flaum Eye Institute and Department of Ophthalmology, University of Rochester, Rochester, New York 14642, USA.
authors: Ying
authors: Y
authors: Jiang
authors: Qian
authors: Q
authors: Ding
authors: Xiaoling
authors: X
authors: Xie
authors: Richard T
authors: RT
authors: Libby
authors: Veronique
authors: V
authors: Lefebvre
authors: Lin
authors: L
authors: Gan
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D055751:SOXC Transcription Factors / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques; D050820:Transcription Factor Brn-3B / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D055751:SOXC Transcription Factors; D050820:Transcription Factor Brn-3B; C117638:Atoh7 protein, mouse; C085559:Pou4f2 protein, mouse; C490793:Sox11 protein, mouse; C489990:Sox4 protein, mouse
keywords: Development; Differentiation; Eye; Gene Knockout; Retina
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