A branched heterochronic pathway directs juvenile-to-adult transition through two LIN-29 isoforms.

Abstract

Robust organismal development relies on temporal coordination of disparate physiological processes. In <i>Caenorhabditis elegans</i>, the heterochronic pathway controls a timely juvenile-to-adult (J/A) transition. This regulatory cascade of conserved proteins and small RNAs culminates in accumulation of the transcription factor LIN-29, which triggers coordinated execution of transition events. We report that two LIN-29 isoforms fulfill distinct functions. Functional specialization is a consequence of distinct isoform expression patterns, not protein sequence, and we propose that distinct LIN-29 dose sensitivities of the individual J/A transition events help to ensure their temporal ordering. We demonstrate that unique isoform expression patterns are generated by the activities of LIN-41 for <i>lin-29a</i>, and of HBL-1 for <i>lin-</i>29<i>b</i>, whereas the RNA-binding protein LIN-28 coordinates LIN-29 isoform activity, in part by regulating both <i>hbl-1</i> and <i>lin-41</i>. Our findings reveal that coordinated transition from juvenile to adult involves branching of a linear pathway to achieve timely control of multiple events.