MLL1 is essential for retinal neurogenesis and horizontal inner neuron integrity

作     者：Brightman, Diana S. Grant, Rachel L. Ruzycki, Philip A. Suzuki, Ray Hennig, Anne K. Chen, Shiming 

作者机构：Washington Univ Dept Ophthalmol & Visual Sci St Louis MO 63130 USA Washington Univ Dept Dev Biol St Louis MO 63130 USA Washington Univ Div Biol & Biomed Sci Mol Cell Biol Grad Program St Louis MO USA Washington Univ Div Biol & Biomed Sci Mol Genet & Genom Grad Program St Louis MO USA Washington Univ Coll Arts & Sci St Louis MO USA Cincinnati Childrens Hosp Med Ctr 3333 Burnet Ave Cincinnati OH 45229 USA 

出 版 物：《SCIENTIFIC REPORTS》 (Sci. Rep.)

年 卷 期：2018年第8卷第1期

页      面：11902-11902页

核心收录：

基　　金：NIH [R01EY012543, T32EY013360, P30EY002687] Research to Prevent Blindness 

摘      要：Development of retinal structure and function is controlled by cell type-specific transcription factors and widely expressed co-regulators. The latter includes the mixed-lineage leukemia (MLL) family of histone methyltransferases that catalyze histone H3 lysine 4 di- and tri-methylation associated with gene activation. One such member, MLL1, is widely expressed in the central nervous system including the retina. However, its role in retinal development is unknown. To address this question, we knocked out Mll1 in mouse retinal progenitors, and discovered that MLL1 plays multiple roles in retinal development by regulating progenitor cell proliferation, cell type composition and neuron-glia balance, maintenance of horizontal neurons, and formation of functional synapses between neuronal layers required for visual signal transmission and processing. Altogether, our results suggest that MLL1 is indispensable for retinal neurogenesis and function development, providing a new paradigm for cell type-specific roles of known histone modifying enzymes during CNS tissue development.