Ras effector switching promotes divergent cell fates in C. elegans vulval patterning.
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.
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Tanya P
TP
Zand
David J
DJ
Reiner
Channing J
CJ
Der
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000166:cytology / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D019070:Cell Lineage; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D008954:Models, Biological; D008969:Molecular Sequence Data; D051880:Receptors, Notch / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014844:Vulva / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D048490:raf Kinases / Q000378:metabolism; D020726:ral Guanine Nucleotide Exchange Factor / Q000737:chemistry / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D051880:Receptors, Notch; D020726:ral Guanine Nucleotide Exchange Factor; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D048490:raf Kinases; D018631:ras Proteins
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