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Science 310 (5752): 1330-1333

Copyright © 2005 by the American Association for the Advancement of Science

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

Andrew S. Yoo1, and Iva Greenwald2*

Abstract: Cell-cell interactions and cross-talk between signaling pathways specify Caenorhabditis elegans vulval precursor cells (VPCs) to adopt a spatial pattern: a central "1°" 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°" 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 down-regulation 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.

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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