N-myc is an essential downstream effector of shh signaling during both normal and neoplastic cerebellar growth Journal Article
| Authors: | Hatton, B. A.; Knoepfler, P. S.; Kenney, A. M.; Rowitch, D. H.; Moreno De Alborán, I.; Olson, J. M.; Eisenman, R. N. |
| Article Title: | N-myc is an essential downstream effector of shh signaling during both normal and neoplastic cerebellar growth |
| Abstract: | We examined the genetic requirements for the Myc family of oncogenes in normal Sonic hedgehog (Shh)-mediated cerebellar granule neuronal precursor (GNP) expansion and in Shh pathway-induced medulloblastoma formation. In GNP-enriched cultures derived from N-mycFl/Fl and c-mycFl/Fl mice, disruption of N-myc, but not c-myc, inhibited the proliferative response to Shh. Conditional deletion of c-myc revealed that, although it is necessary for the general regulation of brain growth, it is less important for cerebellar development and GNP expansion than N-myc. In vivo analysis of compound mutants carrying the conditional N-myc null and the activated Smoothened (ND2:SmoA1) alleles showed, that although granule cells expressing the ND2:SmoA1 transgene are present in the N-myc null cerebellum, no hyperproliferation or tumor formation was detected. Taken together, these findings provide in vivo evidence that N-myc acts downstream of Shh/Smo signaling during GNP proliferation and that N-myc is required for medulloblastoma genesis even in the presence of constitutively active signaling from the Shh pathway. ©2006 American Association for Cancer Research. |
| Keywords: | signal transduction; child; controlled study; nonhuman; cell proliferation; mouse; animals; mice; mice, knockout; allele; animal tissue; cerebellum; cell division; sonic hedgehog protein; animal experiment; animal model; hedgehog proteins; in vivo study; stem cell; kinetics; brain development; genes, myc; medulloblastoma; proto-oncogene proteins c-myc; cerebellar neoplasms; oncogene c myb; brain growth |
| Journal Title: | Cancer Research |
| Volume: | 66 |
| Issue: | 17 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2006-09-01 |
| Start Page: | 8655 |
| End Page: | 8661 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-06-1621 |
| PUBMED: | 16951180 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 54" - "Export Date: 4 June 2012" - "CODEN: CNREA" - "Source: Scopus" |
