The MEP-1 complex is required for repressing germline fate in somatic cells during early development. This putative chromatin-remodeling factor contains the zinc-finger protein MEP-1, the Mi-2 homolog LET-418 and the histone deacetylase HDA-1. We previously proposed that PIE-1, a germline-specific protein that binds this complex, inhibits the MEP-1 complex activity and described a genetic screen to investigate mechanisms of MEP-1 complex regulation. Here, I report the cloning and characterization of one locus identified in this screen.
ex106 was isolated as a strong suppressor of the synMuvB phenotype caused by PIE-1 expression. Since somatic PIE-1 expression phenotypically mimics
mep-1 or
let-418 reduction-of-function, we tested whether
ex106 can also suppress the synMuvB phenotype induced by
mep-1(RNAi),
mep-1(
q660) and
let-418 (RNAi). We found that
ex106 appears not to suppress the synMuv defect under each of those conditions. Similarly, when challenged with RNAi against other synMuvB genes,
ex106 consistently shows no or very little suppression. Thus, wild type activity of
ex106 seems to function upstream or in parallel to MEP-1 complex and probably by increasing its activity. In addition to this phenotype,
ex106 animals exhibit a severe molting defect at all four molts. We observe worms dragging the old cuticle attached at the posterior. Occasionally this defect in early larval stages results in lethality. We found that
ex106 is an allele of a previously identified gene,
nas-37. Four alleles of
nas-37 have been characterized by Jorgensen lab and they all show a molting defect similar to
ex106.
nas-37 encodes a putative extracellular metalloprotease of the Astacin family, sharing domains with BMP1/Tolloid, the regulator of TGF-<font face=symbol>b</font> ligand BMP2. NAS-37 is expressed in the larval hypodermis and the adult seam cell, vulval epithelium and germline. Since
mep-1/let-418 mutations affect the development of these tissues, it seems likely that the proposed genetic interaction between
nas-37 and
mep-1/let-418 occurs at these sites. Given the well established role of Astacin metalloproteases in extracellular signaling, we speculate that NAS-37 may also be a component of such a pathway collaborating with MEP-1 complex and other synMuvB genes restricting the developmental potential in multipotent cells.