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Published Online October 20, 2005
Science DOI: 10.1126/science.1119481

Reports

Submitted on August 29, 2005
Accepted on October 13, 2005

LIN-12/Notch Activation Leads to MicroRNA-Mediated Down-Regulation of Vav in C. elegans

Andrew S. Yoo 1 and Iva Greenwald 2*

1 Integrated Program in Cellular, Molecular, and Biophysical Studies
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.
Iva Greenwald , E-mail: greenwald{at}cancercenter.columbia.edu

Cell-cell interactions and crosstalk between signaling pathways specify C. elegans vulval precursor cells (VPCs) to adopt a spatial pattern: a central "1°" VPC, in which EGFR-MAPK activity is high and LIN-12/Notch activity is low, flanked by two "2°" 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 2° fate. We also identify vav-1, the ortholog of the Vav oncogene, as a target of mir-61, and show that downregulation of VAV-1 promotes lin-12 activity in specifying the 2° 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° VPCs.


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