The homeotlc selector gene
mab-5 is a member of a cluster of homeotic selector genes which is conserved from C. elegans to humans. These genes are expressed in a region specific manner and are required to correctly determine cell fate in the regions in which they are expressed (Wang and Kenyon, unpub.; Clark and Horvitz, personal communication).
mab-5 is expressed in the posterior of the worm and is required in those cells to specify posterior fates. For example,
mab-5 is required in males for the V5 and V6 lineages to produce rays. In males carrying a loss-of-function
mab-5 mutation, the V5 and V6 lineages produce alae instead of rays, just like their anterior homologs. Conversely, ectopic
mab-5 can cause V cells anterior to V5 to produce rays instead of alae (Costa et al., 1988; Kenyon, 1986; Salser. unpub.). In an effort to understand how the wild type pattem of expression is obtained, we decided to screen
mab-5 (
e2088);muls3 animals, which carry a
mab-5 -lacZreporter construct, for mutations which affect the
mab-5 pattern of expression. One of the most striking mutations found,
mu38 ,causes ectopic expression of this construct. In a wild type background the reporter construct is expressed in a number of cells in the posterior of the worm, including the V6 and QL lineages. When newly hatched
mu38 ;muls3 worms are stained, expression appears normal, but when late L1 sare stained, expression extends in the Vn.p cells anteriorly all the way to V1 .pand is also seen in the descendants of QR. There is a concomitant phenotype: the descendants of QR can stay in the posterior (as has been seen in animals carrying a
mab-5 gain-of-function mutation (Salser and Kenyon, 1992)), and in males the V1 -V5lineages make rays instead of alae. These effects are due to ectopic
mab-5 expression, because in the
mu38 ;
mab-5 (
e2088)double mutant they do not occur. The changes can be thought of as homeotic transformations of anterior fates to posterior fates induced by the ectopic
mab-5 .
mu38 worms exhibit other phenotypes as well: they are sometimes Muv, are Unc, and in general are quite sickly. Not all of these phenotypes can be explained by ectopic
mab-5 ,so we decided to see if other genes in the homeotic cluster are misexpressed. Indeed lacZ fusion constructs made with the
lin-39 or
egl-5 genes (which are respectively anterior and posterior to
mab-5 in the cluster (Wang et al., submitted)) are ectopically expressed in a
mu38 background. We have used PCR mapping (Williams et al., 1992) to determine that the
mu38 mutation maps to the right amm of chromsome I. It is closely linked to TCbn2 and
hp4 :0/94 chromosomes examined showed recombination between
mu38 and these markers. The
mu38 mutation causes ectopic expression of at least three genes in the C. elegans homeotic gene cluster. For at least one of these,
mab-5 ,the initial pattern of expression is normal; the gene becomes derepressed later in development (the
lin-39 and
egl-5 expression pattems haven't been checked yet). It appears that the wild type function of the gene mutated by
mu38 is to maintain the homeotic selector genes in a stably repressed state once an initial pattern of expression and repression has been obtained. If this is the case, then
mu38 could be considered to be equivalent to the Drosophila Polycomhgroup of genes (which also are required to maintain homeotic gene repression). The initial pattern of
mab-5 expression changes during development (Salser, unpub.); we are interested in understanding both how the maintenance system revealed by
mu38 works to preserve the initial pattern and whether it is modified to allow for changes in expression.