Vulval induction in C. elegans is an example of the use of an EGF(Epidermal Growth Factor) mediated signal transduction system. At leastfive genes are involved in the negative regulation of vulval induction.
Mutations at the silent locus sli-1 (suppressor of lineage defect) aresufficient to suppress all of the phenotypes associated with hypomorphicalleles of let-23. sli-1 functions to modify the activity of let-23 but muationsat sli-1 do not bypass the requirement for let-23. Based on the phenotypes ofanimals bearing mutations at sli-1 and other genes, sli-1 may function at ornear the let-23 or sem-5 step of vulval differentiation.
Null alleles of the pleiotropic locus unc-101 cause a number of mutantphenotypes including neural defects and suppression of the vulval defectsassociated with some weak let-23 mutations. These unc-101 mutationsinteract with mutations in other genes required for proper vulvaldifferentiation but do not act as generalized suppressors. This locus has beencloned and encodes the C. elegans homolog of the Golgi-associated clathrinadaptor protein AP47.
Animals mutant for both unc-101 and sli-1 display excessive vulvaldifferentiation. Animals mutant at only one of these loci display no vulvalabnormalities. This excessive vulval differentiation requires the inductivesignal and functionallet-23, suggesting that sli-1 and unc-101 function tonegatively regulate the response to the inductive signal, rather than thebasal activity of let-23.
Rare mutant alleles at lin-2, lin-7, and let-23 result in excessive vulvaldifferentiation. These alleles are genetically similar to more common allelesof these genes which result in the failure to differentiate vulval tissue. Thesethree genes apparently are required for the activation of both positive and negative regulators of vulval differentiation.
A number of negative regulators function to control the activity of let-23.At least three pathaways of negative regulation have been geneticallyidentified. These negative regulators act to limit the response to a growth ordifferentiation factor.
