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

Characteristically, the heterochronic genes control the stage-specific timing of developmental events throughout the developing Caenorhaditis elegans larva while gonad development occurs mostly normally. In a few cases, some timing regulators lead to detectable variations in gonad development with little to no effect on fertility. We found that a double mutant of 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. The mechanism of how lin-28 positively influences hbl-1 activity is unresolved. We demonstrate a direct interaction between the RNA-binding protein LIN- 28 and the 5UTR 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-28s regulation of hbl-1 and that some portion of lin-28s effect is independent of lin-46.