Novel gain-of-function alleles demonstrate a role for the heterochronic gene lin-41 in C. elegans male tail tip morphogenesis

Dev Biol. 2006 Sep 1;297(1):74-86. doi: 10.1016/j.ydbio.2006.04.472. Epub 2006 May 6.


To gain an understanding of the genes and mechanisms that govern morphogenesis and its evolution, we have analyzed mutations that disrupt this process in a simple model structure, the male tail tip of the rhabditid nematode C. elegans. During the evolution of rhabditid male tails, there have been several independent changes from tails with rounded tips ("peloderan", as in C. elegans) to those with pointed tips ("leptoderan"). Mutations which produce leptoderan (Lep) tails in C. elegans thus identify candidate genes and pathways in which evolutionary changes could have produced leptoderan tails from peloderan ancestors. Here we report that two novel, gain-of-function (gf) alleles of lin-41 have lesions predicted to affect the N-terminus of the RBCC-domain LIN-41 protein. Both gf alleles cause the tail tip of adult males to retain the pointed shape of the juvenile tails, producing a Lep phenotype that looks like the tails of leptoderan species. Consistent with its role in the heterochronic pathway, we find that lin-41 governs the timing and extent of male tail tip morphogenesis in a dose-dependent manner. Specifically, the Lep phenotype results from a heterochronic delay in the retraction and fusion of the tail tip cells during L4 morphogenesis, such that retraction is not completed before the adult molt. Conversely, we find that tail tip morphogenesis and cell fusions begin precociously at the L3 stage in the reduced-function lin-41 mutant, ma104, resulting in over-retracted male tails in the adult. Because modulated anti-LIN-41 RNAi knockdowns in the gf mutants restore wild-type phenotype, we suggest that the leptoderan phenotype of the gf alleles is due to a higher activity of otherwise normal LIN-41. Additionally, the gf allele is suppressed by the wild-type allele, suggesting that LIN-41 normally regulates itself, possibly by autoubiquitination. We speculate that small changes affecting LIN-41 could have been significant for male tail evolution.

Publication types

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

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Gene Dosage
  • Gene Expression Regulation, Developmental
  • Male
  • Molecular Sequence Data
  • Morphogenesis
  • Mutation
  • Protein Structure, Tertiary
  • Tail / abnormalities
  • Tail / growth & development*
  • Tail / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Caenorhabditis elegans Proteins
  • LIN-41 protein, C elegans
  • Transcription Factors