The C. elegans heterochronic gene lin-28 coordinates the timing of hypodermal and somatic gonadal programs for hermaphrodite reproductive system morphogenesis

Abstract

C. elegans heterochronic genes determine the timing of expression of specific cell fates in particular stages of developing larvae. However, their broader roles in coordinating developmental events across diverse tissues have been less well investigated. Here, we show that loss of lin-28, a central heterochronic regulator of hypodermal development, causes reduced fertility associated with abnormal somatic gonadal morphology. In particular, the abnormal spermatheca-uterine valve morphology of lin-28(lf) hermaphrodites traps embryos in the spermatheca, which disrupts ovulation and causes embryonic lethality. The same genes that act downstream of lin-28 in the regulation of hypodermal developmental timing also act downstream of lin-28 in somatic gonadal morphogenesis and fertility. Importantly, we find that hypodermal expression, but not somatic gonadal expression, of lin-28 is sufficient for restoring normal somatic gonadal morphology in lin-28(lf) mutants. We propose that the abnormal somatic gonadal morphogenesis of lin-28(lf) hermaphrodites results from temporal discoordination between the accelerated hypodermal development and normally timed somatic gonadal development. Thus, our findings exemplify how a cell-intrinsic developmental timing program can also control proper development of other interacting tissues, presumably by cell non-autonomous signal(s). This article has an associated 'The people behind the papers' interview.

Orthologs of the Caenorhabditis elegans heterochronic genes have divergent functions in Caenorhabditis briggsae

“…Cel- lin-28 (0) mutants display a completely penetrant precocious phenotype where they skip cell fates of the L2 and a less penetrant defect of skipping L3 fates ( Ambros and Horvitz 1984 ; Vadla et al 2012 ). They also show an incompletely penetrant fertility problem as a result of spermathecal defects ( Choi and Ambros 2019 ).…”

Orthologs of theC. elegansheterochronic genes have divergent functions inC. briggsae

“…2012). They also show an incompletely penetrant fertility problem as a result of spermathecal defects (Choi and Ambros 2019).…”

“…cel-lin-28(0) mutants display a completely penetrant precocious phenotype where they skip cell fates of the L2, and a less penetrant defect of skipping L3 fates (Ambros and Horvitz 1984;Vadla et al 2012). They also show an incompletely penetrant fertility problem as a result of spermathecal defects (Choi and Ambros 2019).…”

LIN28 Family in Testis: Control of Cell Renewal, Maturation, Fertility and Aging

“…The role of LIN28AB in female cells and tissues has also been explored. The study on C. elegans hermaphrodites showed that loss-of-function LIN28 mutants have oocytes that undergo DNA replication but neither ovulate nor fertilize [42]. The loss of LIN28A expression in the human trophoblast promoted the differentiation of syncytial cells.…”

“…[33] tail development mouse [39] tooth development mouse [40] trophoblast proliferation human 1 and sheep neurogliogenesis Rat and mouse [41] ovulation C. elegans [42] trophoblast differentiation human [15] mesodermal and neural cell fate mouse [39] hippocampal neurogenesis mouse [11] germline stem cells self-renewal human [22] 1 [23] 1 body height human [28][29][30] LIN28B paralog finger length ratio human [31] adiposity human [32] placenta development human [43,44] hematopoietic maturation mouse [13];…”