期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 31, 页码 11579-11583出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0604727103
关键词
Myc; N-Myc deficiency; cerebellum; granule neuron progenitor; cell cycle inhibitor
资金
- NCI NIH HHS [K01-CA-11440, CA-96832, K01 CA114400, R01 CA020525, P01 CA096832, CA-20525, P30 CA021765, CA-21765, CA-72907, R37 CA020525] Funding Source: Medline
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.
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