lin-28 was first characterized as a developmental timing regulator in C. elegans.
lin-28 encodes an RNA-binding protein whose functions include down regulation of the level of
let-7 microRNA. We found that C. elegans
lin-28 loss of function (
lin-28(lf)) mutants exhibit temperature sensitive fertility defects.
lin-28(lf) hermaphrodites have an average brood size of 20 progeny at 20degC (~10% of normal), and are essentially sterile at 25degC. Our data show that
lin-28(lf) mutants not only produce fewer embryos than wild type, but
lin-28(lf) embryos also exhibit about 72% lethality. Some
lin-28(lf) oocytes contain endomitotic DNA, which is a characteristic of defective ovulation. Many
lin-28(lf) embryos become trapped in the spermatheca, suggesting defects in spermathecal exit. We found that these defects are associated with abnormal somatic gonad development of
lin-28(lf) mutants. In particular, an abnormal spermathecal uterine valve structure prevents the proper exit of embryos from the spermatheca into the uterus. Moreover,
lin-28(lf) embryos are more permeable to liphophilic dye than wild type embryos, indicating an abnormal egg shell integrity, which contributes to the embryonic lethality of
lin-28(lf) mutants. Genetically,
let-7 microRNA acts downstream of
lin-28 for hermaphrodite fertility, in that
let-7(lf) partially suppresses the
lin-28(lf) fertility phenotypes, including ovulation, spermathecal exit, embryo production and embryonic lethality. Loss of
lin-29 function, which is positively regulated by
let-7 in heterochronic pathway, also partially rescues
lin-28(lf) fertility defects. We found that
lin-46 is also involved in the fertility function of
lin-28, because
lin-28(lf)
lin-46(lf) double mutants show enhanced fertility phenotypes compared to
lin-28(lf) mutants. Currently, we are determining the timing and tissue that
lin-28 is required for these fertility functions.