| First Author | Zheng MH | Year | 2009 |
| Journal | Mol Brain | Volume | 2 |
| Pages | 38 | PubMed ID | 20017954 |
| Mgi Jnum | J:309104 | Mgi Id | MGI:6756142 |
| Doi | 10.1186/1756-6606-2-38 | Citation | Zheng MH, et al. (2009) The transcription factor RBP-J is essential for retinal cell differentiation and lamination. Mol Brain 2:38 |
| abstractText | 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. |
