Post-transcriptional regulation of the E/Daughterless ortholog HLH-2, negative feedback, and birth order bias during the AC/VU decision in C. elegans

Genes Dev. 2003 Dec 15;17(24):3100-11. doi: 10.1101/gad.1160803.

Abstract

The anchor cell/ventral uterine precursor cell (AC/VU) decision in Caenorhabditis elegans is a canonical example of lin-12/Notch-mediated lateral specification. Two initially equivalent cells interact via the receptor LIN-12 and its ligand LAG-2, so that one becomes the AC and the other a VU. During this interaction, feedback loops amplify a small difference in lin-12 activity, limiting lin-12 transcription to the presumptive VU and lag-2 transcription to the presumptive AC. Here, we find that hlh-2 appears to be required for the VU fate and directly activates lag-2 transcription in the presumptive AC. HLH-2 appears to accumulate selectively in the presumptive AC prior to differential transcription of lin-12 or lag-2, and is therefore the earliest detectable difference between the two cells undergoing the AC/VU decision. The restricted accumulation of HLH-2 to the presumptive AC reflects post-transcriptional down-regulation of HLH-2 in the presumptive VU. Our observations suggest that hlh-2 is regulated as part of the negative feedback that down-regulates lag-2 transcription in the presumptive VU. Finally, we show that the AC/VU decision in an individual hermaphrodite is biased by the relative birth order of the two cells, so that the first-born cell is more likely to become the VU. We propose models to suggest how birth order, HLH-2 accumulation, and transcription of lag-2 may be linked during the AC/VU decision.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Down-Regulation / physiology
  • Feedback, Physiological*
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Developmental / genetics*
  • Genes, Reporter
  • Helix-Loop-Helix Motifs
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mutation / genetics
  • Receptors, Notch
  • Signal Transduction / physiology
  • Transcription, Genetic*
  • Uterus / cytology
  • Uterus / embryology*
  • Uterus / growth & development

Substances

  • Caenorhabditis elegans Proteins
  • Lin-12 protein, C elegans
  • Membrane Proteins
  • Receptors, Notch
  • lag-2 protein, C elegans