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LIN-12/Notch Activation Leads to MicroRNA-Mediated Down-Regulation of Vav in C. elegans
Andrew S. Yoo1 and
Iva Greenwald2*
Cell-cell interactions and cross-talk between signaling pathwaysspecify Caenorhabditis elegans vulval precursor cells (VPCs)to adopt a spatial pattern: a central "1°" VPC, in whichepidermal growth factor receptor (EGFR)–mitogen-activatedprotein kinase (MAPK) activity is high and LIN-12/Notch activityis low, flanked by two "2°" VPCs, in which LIN-12/Notchactivity is high and EGFR-MAPK activity is low. Here, we identifya microRNA gene, mir-61, as a direct transcriptional targetof LIN-12 and show that expression of mir-61 promotes the 2°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-1promotes lin-12 activity in specifying the 2° fate. Ourresults suggest that lin-12, mir-61, and vav-1 form a feedbackloop that helps maximize lin-12 activity in the presumptive2° VPCs.
1 Integrated Program in Cellular, Molecular, and Biophysical Studies, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, 701 West 168th Street, Room 720, New York, NY 10032, USA. 2 Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, 701 West 168th Street, Room 720, New York, NY 10032, USA.
* To whom correspondence should be addressed. E-mail: greenwald{at}cancercenter.columbia.edu
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