Arf-dependent regulation of Pdgf signaling in perivascular cells in the developing mouse eye
| Autor: | J. Derek Thornton, Jerold E. Rehg, Amy C. Martin, Ricardo L.A. Silva, Stephen X. Skapek, Frederique Zindy, David Bertwistle |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Platelet-derived growth factor
Tumor suppressor gene Cell Eye Article General Biochemistry Genetics and Molecular Biology Mural cell Receptor Platelet-Derived Growth Factor beta Mice chemistry.chemical_compound Proto-Oncogene Proteins Tumor Suppressor Protein p14ARF medicine Animals Molecular Biology Cyclin-Dependent Kinase Inhibitor p16 Cell Proliferation Mice Knockout General Immunology and Microbiology biology Cell growth General Neuroscience Nuclear Proteins Proto-Oncogene Proteins c-mdm2 Proto-Oncogene Proteins c-sis medicine.anatomical_structure chemistry biology.protein Cancer research Pericyte Tumor Suppressor Protein p53 Signal transduction Platelet-derived growth factor receptor Signal Transduction |
| Zdroj: | The EMBO Journal. 24:2803-2814 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.1038/sj.emboj.7600751 |
| Popis: | We have established that the Arf tumor suppressor gene regulates mural cell biology in the hyaloid vascular system (HVS) of the developing eye. In the absence of Arf, perivascular cells accumulate within the HVS and prevent its involution. We now demonstrate that mural cell accumulation evident at embryonic day (E) 13.5 in Arf(-/-) mice was driven by excess proliferation at E12.5, when Arf expression was detectable in vitreous pericyte-like cells. Their expression of Arf overlapped with Pdgf receptor beta (Pdgfrbeta), which is essential for pericyte accumulation in the mouse. In cultured cells, p19Arf decreased Pdgfrbeta and blocked Pdgf-B-driven proliferation independently of Mdm2 and p53. The presence of a normal Arf allele correlated with decreased Pdgfrbeta in the embryonic vitreous. Pdgfrbeta was required for vitreous cell accumulation in the absence of Arf. Our findings demonstrate a novel, p53- and Mdm2-independent function for p19Arf. Instead of solely sensing excessive mitogenic stimuli, developmental cues induce Arf to block Pdgfrbeta-dependent signals and prevent the accumulation of perivascular cells selectively in a vascular bed destined to regress. |
| Databáze: | OpenAIRE |
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