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The transcription factor RBP-J is essential for retinal cell differentiation and lamination
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...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804697/ https://www.ncbi.nlm.nih.gov/pubmed/20017954 http://dx.doi.org/10.1186/1756-6606-2-38 |
Sumario: | 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 β-catenin deficient retina. Indeed, we found that these rosettes aligned with gaps in β-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 β-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 β-catenin. |
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