Ras effector switching promotes divergent cell fates in C. elegans vulval patterning

Dev Cell. 2011 Jan 18;20(1):84-96. doi: 10.1016/j.devcel.2010.12.004.

Abstract

The C. elegans vulva is patterned by epidermal growth factor (EGF) activation of Ras to control 1° fate, and 1° fate induces antagonistic Notch-dependent 2° fate. Furthermore, a spatial EGF gradient, in addition to inducing 1° fate, directly contributes to 2° fate via an unknown pathway. We find that in addition to its canonical effector, Raf, vulval Ras utilizes an exchange factor for the Ral small GTPase (RalGEF), such that Ras-RalGEF-Ral antagonizes Ras-Raf pro-1° fate activity. Consistent with its restricted expression pattern, Ral participates in EGF pro-2° activity. Thus, we have delineated a Ras effector-switching mechanism whereby position within the morphogen gradient dictates that Ras effector usage is switched to RalGEF from Raf to promote 2° instead of 1° fate. Our observations define the utility of Ras effector switching during normal development and may provide a possible mechanistic basis for cell and cancer-type differences in effector dependency and activation.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Body Patterning*
  • Caenorhabditis elegans / chemistry
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Lineage*
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / metabolism
  • Female
  • Models, Biological
  • Molecular Sequence Data
  • Receptors, Notch / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Vulva / cytology*
  • Vulva / growth & development*
  • Vulva / metabolism
  • raf Kinases / metabolism
  • ral Guanine Nucleotide Exchange Factor / chemistry
  • ral Guanine Nucleotide Exchange Factor / metabolism
  • ras Proteins / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Receptors, Notch
  • ral Guanine Nucleotide Exchange Factor
  • Epidermal Growth Factor
  • ErbB Receptors
  • raf Kinases
  • ras Proteins

Associated data

  • RefSeq/NP_497689