Integration of semaphorin-2A/MAB-20, ephrin-4, and UNC-129 TGF-beta signaling pathways regulates sorting of distinct sensory rays in C. elegans

Dev Cell. 2004 Mar;6(3):383-95. doi: 10.1016/s1534-5807(04)00057-7.


Semaphorins and ephrins are axon guidance cues. In C. elegans, semaphorin-2a/mab-20 and ephrin-4/efn-4/mab-26 also regulate cell sorting to form distinct rays in the male tail. Several erf (enhancer of ray fusion) mutations were identified in a mab-20 enhancer screen. Mutants of plexin-2 (plx-2) and unc-129, which encodes an axon guiding TGF-beta, were also found to be erfs. Genetic analyses show that plx-2 and mab-20 function in the same pathway, as expected if PLX-2 is a receptor for MAB-20. Surprisingly, MAB-20 also signals in a parallel pathway that requires efn-4. This signal utilizes a non-plexin receptor. The expression of plx-2, efn-4, and unc-129 in subsets of 3-cell sensory ray clusters likely mediates the ray-specific cell sorting functions of the ubiquitously expressed mab-20. We present a model for the integrated control of TGF-beta, semaphorin, and ephrin signaling in the sorting of cell clusters into distinct rays in the developing male tail.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chi-Square Distribution
  • Chromosome Mapping / methods
  • Cloning, Molecular
  • DNA Mutational Analysis
  • Enhancer Elements, Genetic
  • Ephrin-A4 / genetics
  • Ephrin-A4 / physiology*
  • Ephrins / physiology
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins
  • Immunohistochemistry / methods
  • Luminescent Proteins / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Models, Molecular
  • Mutagenesis, Insertional / methods
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Sense Organs / physiology*
  • Sequence Analysis, DNA
  • Signal Transduction / physiology*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / physiology*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism


  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • EFN-4 protein, C elegans
  • Ephrin-A4
  • Ephrins
  • Luminescent Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Transforming Growth Factor beta
  • UNC-129 protein, C elegans
  • Xenopus Proteins
  • mab-20 protein, C elegans
  • Green Fluorescent Proteins
  • PlK2 protein, Xenopus
  • Protein-Serine-Threonine Kinases