| First Author | Kenney AM | Year | 2004 |
| Journal | Development | Volume | 131 |
| Issue | 1 | Pages | 217-28 |
| PubMed ID | 14660435 | Mgi Jnum | J:87230 |
| Mgi Id | MGI:2683944 | Doi | 10.1242/dev.00891 |
| Citation | Kenney AM, et al. (2004) Hedgehog and PI-3 kinase signaling converge on Nmyc1 to promote cell cycle progression in cerebellar neuronal precursors. Development 131(1):217-28 |
| abstractText | Neuronal precursor cells in the developing cerebellum require activity of the sonic hedgehog (Shh) and phosphoinositide-3-kinase (PI3K) pathways for growth and survival. Synergy between the Shh and PI3K signaling pathways are implicated in the cerebellar tumor medulloblastoma. Here, we describe a mechanism through which these disparate signaling pathways cooperate to promote proliferation of cerebellar granule neuron precursors. Shh signaling drives expression of mRNA encoding the Nmyc1 oncoprotein (previously N-myc), which is essential for expansion of cerebellar granule neuron precursors. The PI3K pathway stabilizes Nmyc1 protein via inhibition of GSK3-dependent Nmyc1 phosphorylation and degradation. The effects of PI3K activity on Nmyc1 stabilization are mimicked by insulin-like growth factor, a PI3K agonist with roles in central nervous system precursor growth and tumorigenesis. These findings indicate that Shh and PI3K signaling pathways converge on N-Myc to regulate neuronal precursor cell cycle progression. Furthermore, they provide a rationale for therapeutic targeting of PI3K signaling in medulloblastoma. |
