Journal
SCIENCE
Volume 310, Issue 5752, Pages 1330-1333Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1119481
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Funding
- NCI NIH HHS [CA095389, R01 CA095389-06A1, R01 CA095389-05, R01 CA095389, R01 CA095389-03, R01 CA095389-02, R01 CA095389-01A1, R01 CA095389-04] Funding Source: Medline
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Cell-cell interactions and cross-talk between signaling pathways specify Caenorhabditis elegans vulval precursor cells (VPCs) to adopt a spatial pattern: a central 1 degrees VPC, in which epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) activity is high and LIN-12/Notch activity is low, flanked by two 2 degrees VPCs, in which LIN-12/Notch activity is high and EGFR-MAPK activity is low. Here, we identify a microRNA gene, mir-61, as a direct transcriptional target of LIN-12 and show that expression of mir-61 promotes the 20 fate. We also identify vav-1, the ortholog of the Vav oncogene, as a target of mir-61, and show that down-regulation of VAV-1 promotes lin-12 activity in specifying the 2 degrees fate. Our results suggest that lin-12, mir-61, and vav-1 form a feedback loop that helps maximize lin-12 activity in the presumptive 2 degrees VPCs.
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