title: The transcription factor RBP-J is essential for retinal cell differentiation and lamination.
abstract: BACKGROUND
  The highly ordered vertebrate retina is composed of seven cell types derived from a common pool of retinal progenitor cells (RPCs), and is a good model for the studies of cell differentiation and interaction during neural development. Notch signaling plays a pivotal role in retinogenesis in mammals, but the full scope of the functions of Notch pathway, and the underlying molecular mechanisms, remain unclear.
  
  
  RESULTS
  In this study, we conditionally knocked out RBP-J, the critical transcription factor downstream to all four Notch receptors, in RPCs of mouse retina at different developmental stages. Disruption of RBP-J at early retinogenesis resulted in accelerated RPCs differentiation, but only photoreceptors and ganglion cells were overrepresented, with other neuronal populations diminished. Similarly, deletion of RBP-J at early postnatal days also led to overproduction of photoreceptors, suggesting that RBP-J governed RPCs specification and differentiation through retinogenesis. In all the RBP-J deletion models, the retinal laminar structures were distorted by the formation of numerous rosette-like structures, reminiscent of beta-catenin deficient retina. Indeed, we found that these rosettes aligned with gaps in beta-catenin expression at the apical surface of the retina. By in vivo electroporation-mediated transfection, we demonstrated that lamination defects in RBP-J deficient retinae were rescued by overexpressing beta-catenin.
  
  
  CONCLUSIONS
  Our data indicate that RBP-J-mediated canonical Notch signaling governs retinal cell specification and differentiation, and maintains retinal lamination through the expression of beta-catenin.
authors.affiliation: Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an 710032, China. zhengmh1980@gmail.com
authors.forename: Min-Hua
authors.initials: MH
authors.lastname: Zheng
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Zhe
authors.initials: Z
authors.lastname: Pei
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
authors.forename: Hua
authors.initials: H
authors.lastname: Han
authors.forename: Yu-Qiang
authors.initials: YQ
authors.lastname: Ding
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D017353:Gene Deletion; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000172:deficiency / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D038081:Organogenesis; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology; D012160:Retina / Q000378:metabolism* / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D014157:Transcription Factors; D051176:beta Catenin; C045073:Cre recombinase; D019426:Integrases