| Title | Rbpj cell autonomous regulation of retinal ganglion cell and cone photoreceptor fates in the mouse retina. | | Author(s) | Riesenberg AN, Liu Z, Kopan R, Brown NL | | Institution | Division of Developmental Biology, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA. | | Source | J Neurosci 2009 Oct 14; 29(41):12865-77. | | MeSH | Animals
Animals, Newborn
Basic Helix-Loop-Helix Transcription Factors
Cell Differentiation
Cell Proliferation
Disease Models, Animal
Embryo, Mammalian
Eye Diseases, Hereditary
Gene Expression Regulation, Developmental
Green Fluorescent Proteins
Homeodomain Proteins
Immunoglobulin J Recombination Signal Sequence-Binding Protein
Mice
Mice, Transgenic
Mutation
Nerve Tissue Proteins
Receptors, Notch
Repressor Proteins
Retina
Retinal Cone Photoreceptor Cells
Retinal Ganglion Cells
Retinal Rod Photoreceptor Cells
Transcription Factor Brn-3B
Transcription Factors
| | Abstract | Vertebrate retinal progenitor cells (RPCs) are pluripotent, but pass through competence states that progressively restrict their developmental potential (Cepko et al., 1996; Livesey and Cepko, 2001; Cayouette et al., 2006). In the rodent eye, seven retinal cell classes differentiate in overlapping waves, with RGCs, cone photoreceptors, horizontals, and amacrines forming predominantly before birth, and rod photoreceptors, bipolars, and Müller glia differentiating postnatally. Both intrinsic and extrinsic factors regulate each retinal cell type (for review, see Livesey and Cepko, 2001). Here, we conditionally deleted the transcription factor Rbpj, a critical integrator of multiple Notch signals (Jarriault et al., 1995; Honjo, 1996; Kato et al., 1997; Han et al., 2002), during prenatal mouse retinal neurogenesis. Removal of Rbpj caused reduced proliferation, premature neuronal differentiation, apoptosis, and profound mispatterning. To determine the cell autonomous requirements for Rbpj during RGC and cone formation, we marked Cre-generated retinal lineages with GFP expression, which showed that Rbpj autonomously promotes RPC mitotic activity, and suppresses RGC and cone fates. In addition, the progressive loss of Rbpj-/- RPCs resulted in a diminished progenitor pool available for rod photoreceptor formation. This circumstance, along with the overproduction of Rbpj-/- cones, revealed that photoreceptor development is under homeostatic regulation. Finally, to understand how the Notch pathway regulates the simultaneous formation of multiple cell types, we compared the RGC and cone phenotypes of Rbpj to Notch1 (Jadhav et al., 2006b; Yaron et al., 2006), Notch3, and Hes1 mutants. We found particular combinations of Notch pathway genes regulate the development of each retinal cell type. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, N.I.H., Extramural
| | PubMed ID | 19828801 |
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