Abstract
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.
Original language | English (US) |
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Pages (from-to) | 11579-11583 |
Number of pages | 5 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 103 |
Issue number | 31 |
DOIs | |
State | Published - Aug 1 2006 |
Keywords
- Cell cycle inhibitor
- Cerebellum
- Granule neuron progenitor
- Myc
- N-Myc deficiency
ASJC Scopus subject areas
- Genetics
- General