A temporal sequence of heterochronic gene activities promotes stage-specific developmental events inC. elegans

Abstract

AbstractThe heterochronic genes of the nematodeCaenorhabditis eleganscontrol the succession of postembryonic developmental events. The four core heterochronic geneslin-14, lin-28, hbl-1,andlin-41act in a sequence to specify cell fates specific to each of the four larval stages. It was previously shown thatlin-14has two activities separated in time that promote L1 and L2 developmental events, respectively. Using the auxin-inducible degron system, we find thatlin-28andhbl-1each have two activities that control L2 and L3 events which are also separated in time. Relative to events they control, bothlin-28andhbl-1appear to act just prior to or concurrently with events of the L2. Relative to each other,lin-28andhbl-1appear to act simultaneously. By contrast, thelin-14activity controlling L2 events precedes those oflin-28andhbl-1controlling the same events, suggestinglin-14’s regulation oflin-28is responsible for the delay. Likewise, the activities oflin-28andhbl-1controlling L3 fates act well in advance of those fates, suggesting a similar regulatory gap.lin-41acts early in the L3 to affect fates of the L4, although it was not possible to determine whether it too has two temporally separated activities. We also uncovered a feedback phenomenon that prevents the reactivation of heterochronic gene activity late in development after it has been down-regulated. This study places the heterochronic gene activities into a timeline of postembryonic development relative to one another and to the developmental events whose timing they control.