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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."xsd:string
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http://purl.uniprot.org/citations/20017954http://purl.uniprot.org/core/author"Gao F."xsd:string
http://purl.uniprot.org/citations/20017954http://purl.uniprot.org/core/author"Shi M."xsd:string
http://purl.uniprot.org/citations/20017954http://purl.uniprot.org/core/author"Pei Z."xsd:string
http://purl.uniprot.org/citations/20017954http://purl.uniprot.org/core/author"Han H."xsd:string
http://purl.uniprot.org/citations/20017954http://purl.uniprot.org/core/author"Ding Y.Q."xsd:string
http://purl.uniprot.org/citations/20017954http://purl.uniprot.org/core/author"Zheng M.H."xsd:string
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http://purl.uniprot.org/citations/20017954http://purl.uniprot.org/core/title"The transcription factor RBP-J is essential for retinal cell differentiation and lamination."xsd:string
http://purl.uniprot.org/citations/20017954http://purl.uniprot.org/core/volume"2"xsd:string
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