| First Author | Zindy F | Year | 2006 |
| Journal | Proc Natl Acad Sci U S A | Volume | 103 |
| Issue | 31 | Pages | 11579-83 |
| PubMed ID | 16864777 | Mgi Jnum | J:111800 |
| Mgi Id | MGI:3654866 | Doi | 10.1073/pnas.0604727103 |
| Citation | Zindy F, et al. (2006) N-Myc and the cyclin-dependent kinase inhibitors p18Ink4c and p27Kip1 coordinately regulate cerebellar development. Proc Natl Acad Sci U S A 103(31):11579-83 |
| abstractText | Conditional N-Myc deletion limits the proliferation of granule neuron progenitors (GNPs), perturbs foliation, and leads to reduced cerebellar mass. We show that c-Myc mRNA levels increase in N-Myc-null GNPs and that simultaneous deletion of both c- and N-Myc exacerbates defective cerebellar development. Moreover, N-Myc loss has been shown to trigger the precocious expression of two cyclin-dependent kinase inhibitors, Kip1 and Ink4c, in the cerebellar primordium. We now further demonstrate that the engineered disruption of the Kip1 and Ink4c genes in N-Myc-null cerebella partially rescues GNP cell proliferation and cerebellar foliation. These results provide definitive genetic evidence that expression of N-Myc and concomitant down-regulation of Ink4c and Kip1 contribute to the proper development of the cerebellum. |
