title: Transient Expression of Fez Family Zinc Finger 2 Protein Regulates the Brn3b Gene in Developing Retinal Ganglion Cells.
abstract: Retinal ganglion cells (RGCs) are projection neurons in the neural retina that relay visual information from the environment to the central nervous system. The early expression of MATH5 endows the post-mitotic precursors with RGC competence and leads to the activation ofBrn3bthat marks committed RGCs. Nevertheless, this fate commitment process and, specifically, regulation ofBrn3bremain elusive. To explore the molecular mechanisms underlying RGC generation in the mouse retina, we analyzed the expression and function of Fez family zinc finger 2 (FEZF2), a transcription factor critical for the development of projection neurons in the cerebral cortex.Fezf2mRNA and protein were transiently expressed at embryonic day 16.5 in the inner neuroblast layer and the prospective ganglion cell layer of the retina, respectively. Knockout ofFezf2in the developing retina reduced BRN3B+ cells and increased apoptotic cell markers.Fezf2knockdown by retinalin uteroelectroporation diminished BRN3B but not the coexpressed ISLET1 and BRN3A, indicating that the BRN3B decrease was the cause, not the result, of the overall reduction of BRN3B+ RGCs in theFezf2knockout retina. Moreover, the mRNA and promoter activity ofBrn3bwere increasedin vitroby FEZF2, which bound to a 5' regulatory fragment in theBrn3bgenomic locus. These results indicate that transient expression ofFezf2in the retina modulates the transcription ofBrn3band the survival of RGCs. This study improves our understanding of the transcriptional cascade required for the specification of RGCs and provides novel insights into the molecular basis of retinal development.
authors: From the School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China, the China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang 325000, China, the Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325000, China, the Clinical Laboratory of LiShui People's Hospital, Sixth Affiliated Hospital, Wenzhou Medical University, LiShui, Zhejiang 323000, China.
authors: Chunsheng
authors: C
authors: Qu
authors: From the School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China, the China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang 325000, China, the Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325000, China.
authors: Dandan
authors: D
authors: Bian
authors: From the School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China, the China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang 325000, China, the Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325000, China.
authors: Xue
authors: X
authors: Li
authors: From the School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China, the China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang 325000, China, the Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325000, China.
authors: Jian
authors: J
authors: Xiao
authors: From the School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China, the China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang 325000, China, the Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325000, China.
authors: Chunping
authors: C
authors: Wu
authors: the Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, and.
authors: Yue
authors: Y
authors: Li
authors: From the School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China, the China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang 325000, China, the Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325000, China.
authors: Tian
authors: T
authors: Jiang
authors: From the School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China, the China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang 325000, China, the Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325000, China.
authors: Xiangtian
authors: X
authors: Zhou
authors: From the School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China, the China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang 325000, China, the Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325000, China.
authors: Jia
authors: J
authors: Qu
authors: From the School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China, the China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of China, Wenzhou, Zhejiang 325000, China, the Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang 325000, China, jgchen@mail.eye.ac.cn jiesbooks@gmail.com.
authors: Jie-Guang
authors: JG
authors: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D050820:Transcription Factor Brn-3B / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C085559:Pou4f2 protein, mouse; D012333:RNA, Messenger; D050820:Transcription Factor Brn-3B; C412364:Zfp312 protein, mouse
keywords: Brn3b; Fezf2; gene expression; gene knockout; in utero electroporation; mouse; neurodevelopment; retinal ganglion cells; transcription regulation