Reciprocal signaling by Wnt and Notch specifies a muscle precursor in the C. elegans embryo

Development. 2017 Feb 1;144(3):419-429. doi: 10.1242/dev.145391. Epub 2017 Jan 3.

Abstract

The MS blastomere produces one-third of the body wall muscles (BWMs) in the C. elegans embryo. MS-derived BWMs require two distinct cell-cell interactions, the first inhibitory and the second, two cell cycles later, required to overcome this inhibition. The inductive interaction is not required if the inhibitory signal is absent. Although the Notch receptor GLP-1 was implicated in both interactions, the molecular nature of the two signals was unknown. We now show that zygotically expressed MOM-2 (Wnt) is responsible for both interactions. Both the inhibitory and the activating interactions require precise spatiotemporal expression of zygotic MOM-2, which is dependent upon two distinct Notch signals. In a Notch mutant defective only in the inductive interaction, MS-derived BWMs can be restored by preventing zygotic MOM-2 expression, which removes the inhibitory signal. Our results suggest that the inhibitory interaction ensures the differential lineage specification of MS and its sister blastomere, whereas the inductive interaction promotes the expression of muscle-specifying genes by modulating TCF and β-catenin levels. These results highlight the complexity of cell fate specification by cell-cell interactions in a rapidly dividing embryo.

Keywords: Body wall muscles; C. elegans; MS blastomere; Notch; Wnt; glp-1; mom-2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Blastomeres / cytology
  • Blastomeres / metabolism
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Lineage / genetics
  • Cell Lineage / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Embryonic Induction / genetics
  • Embryonic Induction / physiology
  • GATA Transcription Factors / genetics
  • GATA Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Genes, Helminth
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Models, Biological
  • Muscles / embryology
  • Mutation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Sodium Channels / genetics
  • Sodium Channels / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • TCF Transcription Factors / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / genetics
  • Wnt Signaling Pathway / physiology
  • Zygote / cytology
  • Zygote / metabolism
  • beta Catenin / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • END-1 protein, C elegans
  • GATA Transcription Factors
  • Glp-1 protein, C elegans
  • Intracellular Signaling Peptides and Proteins
  • MOM-2 protein, C elegans
  • RNA, Messenger
  • Receptors, Notch
  • Sodium Channels
  • T-Box Domain Proteins
  • TBX-35 protein, C elegans
  • TCF Transcription Factors
  • Transcription Factors
  • Wnt Proteins
  • apx-1 protein, C elegans
  • beta Catenin
  • ref-1 protein, C elegans
  • skn-1 protein, C elegans