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

Elife. 2020 Mar 30:9:e53387. doi: 10.7554/eLife.53387.


Robust organismal development relies on temporal coordination of disparate physiological processes. In Caenorhabditis elegans, 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 lin-29a, and of HBL-1 for lin-29b, whereas the RNA-binding protein LIN-28 coordinates LIN-29 isoform activity, in part by regulating both hbl-1 and lin-41. Our findings reveal that coordinated transition from juvenile to adult involves branching of a linear pathway to achieve timely control of multiple events.

Keywords: C. elegans; developmental biology; developmental timing; epidermis; heterochronic; molt; puberty; terminal differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Differentiation
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental*
  • Life Cycle Stages
  • Phenotype
  • Protein Isoforms
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • LIN-29 protein, C elegans
  • LIN-41 protein, C elegans
  • Protein Isoforms
  • Transcription Factors