Lhx2 Is an Essential Factor for Retinal Gliogenesis and Notch Signaling

• DOI: 10.1523/jneurosci.3145-15.2016
• Publication Date: 2016-02-24T22:37:53Z
• Authors: Jimmy de Melo; Cristina Zibetti; Brian S. Clark; Woochang Hwang; Ana L. Miranda-An...; Jiang Qian; Seth Blackshaw
• Keywords: Gliogenesis; HES1; Muller glia; Cell fate determination

Müller glia (MG) are the only glial cell type produced by neuroepithelial progenitor cells that generate vertebrate retina. MG required to maintain retinal homeostasis and support survival of neurons. Furthermore, in certain classes, function as adult stem cells, mediating regeneration response injury. However, mechanisms regulate development poorly understood because there is considerable overlap gene expression between differentiated MG. We show LIM homeodomain transcription factor Lhx2 for mouse Temporally controlled knock-out studies reveal a requirement during all stages development, ranging from proliferation gliocompetent progenitors, activation Müller-specific expression, terminal differentiation morphological features. regulates gliogenesis part regulating directly Notch pathway genes including Notch1 , Dll1 Dll3 gliogenic factors such Hes1 Hes5 Sox8 Rax . Conditional resulted rapid downregulation loss signaling. further demonstrate induced misexpression potently transcriptional effector requires expression. These results indicate not signaling components, but also acts together with drive specification differentiation. SIGNIFICANCE STATEMENT radial located retina essential found be expressed both Using conditional knock-outs, we development. components pathway, which promotes gliogenesis, well multiple factors. Hes5-dependent gliogenesis. This study identifies central regulator Notch-dependent Notch-independent