Fig. 4.

vav-1 is a negative regulator of lin-12 activity in the VPCs. (A) vav-1(RNAi) enhances lin-12 activity in VPCs. The average percentage of worms with a Multivulva (Muv) phenotype (three or more pseudovulvae) on three independent plates is shown. For lin-12(n676); vav-1(RNAi), the number of Muv hermaphrodites out of the total per plate was 50 out of 109, 49 out of 112, and 54 out of 125, with the control lin-12(n676); gfp(RNAi) values of 8 out of 157, 17 out of 168, and 18 out of 152. For lin-12(n379); vav-1(RNAi), the numbers were 20 out of 187, 25 out of 208, and 13 out of 167, with lin-12(n379); gfp(RNAi) values of 1 out of 204, 1 out of 228, and 2 out of 225. Error bar indicates SD. **P < 0.01 by Student’s t test. (B) mir-61, vav-1, and the circuitry underlying specification of the 2° VPC fate. Activation of the EGFR-MAPK pathway in P6.p has two consequences for lateral signaling: transcription of the three Delta/Serrate/LAG-2 (DSL) ligands that constitute the lateral signal, which activates LIN-12/Notch in P5.p and P7.p (27), and internalization of LIN-12, which is necessary for lateral signal activity (28). Activation of LIN-12 in P5.p and P7.p activates a set of lst genes that counteract the EGFR-MAPK pathway (3), and mir-61, which posttranscriptionally down-regulates VAV-1 to promote lin-12 activity.