Somatic gonad morphogenesis in C. elegans requires the heterochronic pathway acting through HBL-1.

Abstract

The heterochronic genes are known for acting in succession to control the timing of stage-specific events of the developing Caenorhabditis elegans larva. While most heterochronic mutants have normal gonad development, in a few cases defective timing regulators lead to variations in gonad development, although with little to no effect on fertility. We found that a double mutant of two heterochronic genes, a lin-28 null allele and hbl-1 hypomorphic allele, results in a catastrophic failure of gonad morphogenesis resulting in sterility. This defect includes a high-penetrance disruption of normal gonad arm migration as well as frequent absence of one or both spermathecae. We demonstrate that the abnormal gonad morphology and novel sterility phenotype is ultimately due to loss of hbl-1 activity in larval development. To clarify the mechanism of how lin-28 positively influences hbl-1 activity, we demonstrate a direct interaction between the RNA-binding protein LIN-28 and the 5'UTR of lin-46, and in turn, a direct interaction between LIN-46 and two zinc fingers of HBL-1. Nevertheless, our genetic analysis indicates that lin-46 accounts for only part of lin-28's regulation of hbl-1 and that some portion of lin-28's effect is independent of lin-46.