lin-28 was first characterized as a developmental timing regulator in C. elegans.
lin-28 loss of function mutants skip L2 specific fates of the lateral hypodermal and vulva cell lineages, causing precocious development of these tissues.
lin-28(lf) hermaphrodites also exhibit reduced fertility. Our data show that
lin-28(lf) mutants not only produce far fewer embryos than wild type, but also ~72% embryos from
lin-28(lf) hermaphrodites are not viable at 25oC. We found that reduced fertility in
lin-28(lf) is associated with abnormal morphogenesis of the somatic gonad, including defective structure of the spermathecal-uterine valve (Sp-Ut valve), which connects the spermatheca to the uterus in wild type animals. Consequently, many
lin-28(lf) embryos become trapped in the spermatheca after fertilization. Due to this blockage of spermathecal exit, some
lin-28(lf) oocytes contain endomitotic DNA, a characteristic of defective ovulation. 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 lethality of embryos produced by
lin-28(lf) hermaphrodites. We found that the genes previously shown to act downstream of
lin-28 in the regulation of lateral hypodermal and vulval developmental timing also act downstream of
lin-28 in Sp-Ut valve morphogenesis and fertility. For example, loss of
let-7,
lin-29 or
lin-46 suppresses abnormal Sp-Ut valve phenotype and fertility defects in
lin-28(lf) mutants. Also, wild type animals treated with
hbl-1 RNAi also exhibit Sp-Ut valve morphogenesis defects similar to
lin-28(lf) mutants. However, we found that the development of the somatic gonad, including the Sp-Ut valve, does not appear to be precocious in
lin-28(lf) mutants, unlike the hypodermis. Moreover, somatic gonadal expression of
lin-28 is not sufficient for rescuing Sp-Ut valve defects in
lin-28(lf) mutants. Therefore we hypothesize that the abnormal somatic gonad morphogenesis of
lin-28(lf) hermaphrodites results from temporal discoordination between the precocious development of hypodermal tissues and the essentially normal timing of somatic gonad development. We are now using tissue-specific rescue strategies to further investigate the anatomical focus of action of
lin-28 in the control of somatic gonadal morphogenesis.