The
lin-57(
ve18) mutation causes the precocious terminal differentiation of the lateral hypodermal seam cells during the L3 molt. In
lin-57;
lin-29 double mutants, the hypodermal seam cells never terminally differentiate, indicating that
lin-57 acts through
lin-29 to control this event. The
ve18 mutation affects a splice site and appears to represent a reduction-of-function allele. Progeny of
lin-57 RNAi treated animals exhibit two main phenotypes: precocious seam cell terminal differentiation or embryonic lethality. Because only one
lin-57 splice form has been detected and there are no genes sharing high sequence similarity to
lin-57, this result suggests that the
lin-57 null phenotype is embryonic lethality. One possibility is that
lin-57 may play two roles in development, one during embryogenesis and one during the L3 stage. Non-complementation screens have yielded a candidate
lin-57 allele (
ve54 ) which is embryonic lethal when homozygous.
lin-57 encodes a HUNCHBACK-like protein (a.k.a. HBL-1; Fay et al., 1999) which contains nine zinc finger motifs, six of which share similarity to the six D. melanogaster HUNCHBACK zinc fingers. Thus,
lin-57 is likely to act as a transcriptional regulator within the heterochronic gene pathway to control the time of seam cell terminal differentiation. Non-rescuing
lin-57:gfp constructs are expressed during embryogenesis through the L3 stage. Expression decreases during the L4 stage and is not detected in adult animals. This regulation appears to be achieved post-transcriptionally via the
lin-57 3’ UTR since similar constructs containing the
unc-54 3' UTR are expressed during all stages of development. The
lin-57 3' UTR contains eight putative binding sites for the 21nt
let-7 regulatory RNA (Reinhart et al., 2000). A subset of these sites are conserved in C. briggsae and C. remanei . The temporal expression pattern of
let-7 (late L3-Adult) suggests that the downregulation of
lin-57 could be mediated by
let-7 . Constructs bearing point mutations in the putative
let-7 binding sites are now being tested for their ability to cause
lin-57 mis-regulation. We also noted a single putative
lin-4 binding site in the
lin-57 3’ UTR. However, the functional significance of this site is unclear;
lin-4 is epistatic to
lin-57 which suggests that
lin-57 is not a downstream target of the
lin-4 gene. Fay, D., H. Stanley, M. Han and W. Wood (1999). Developmental Biology 205 : 240-253. Reinhart, B., F. Slack, M. Basson, A. Pasquinelli, J. Bettinger, A. Rougvie, H. Horvitz and G. Ruvkun (2000). Nature 403 : 901-906.