The “Negative Signal” from hyp7 is now likely to be inhibition of lin-3 expression by synmuv proteins (Cui et al., Dev Cell 2006; Andersen and Horvitz, Development 2007). In the absence of synmuv function, lin-3 is expressed from hyp7 (and possibly other sites) and simulates LET-23 in the VPCs. Synmuv backgrounds (for example, lin-15A-B-) have been used to create a uniform level of LET-23 activation; this new finding does not affect any of the conclusions using these strains, and provides a satisfactory mechanistic understandig of why lin-15 has been so useful!. With respect to mechanism of synmuv action, these results provide a bona fide target of synmuv represssion; this is very exciting.
The discussion of the negative signal will be fixed in the revised version of the Vulva Development Chapter. -Paul