RRC ID 59549
Author Maxeiner S, Grolleman J, Schmid T, Kammenga J, Hajnal A.
Title The hypoxia-response pathway modulates RAS/MAPK-mediated cell fate decisions in Caenorhabditis elegans.
Journal Life Sci Alliance
Abstract Animals need to adjust many cellular functions to oxygen availability to adapt to changing environmental conditions. We have used the nematode Caenorhabditis elegans as a model to investigate how variations in oxygen concentrations affect cell fate specification during development. Here, we show that several processes controlled by the conserved RTK/RAS/MAPK pathway are sensitive to changes in the atmospheric oxygen concentration. In the vulval precursor cells (VPCs), the hypoxia-inducible factor HIF-1 activates the expression of the nuclear hormone receptor NHR-57 to counteract RAS/MAPK-induced differentiation. Furthermore, cross-talk between the NOTCH and hypoxia-response pathways modulates the capability of the VPCs to respond to RAS/MAPK signaling. Lateral NOTCH signaling positively regulates the prolyl hydroxylase EGL-9, which promotes HIF-1 degradation in uncommitted VPCs and permits RAS/MAPK-induced differentiation. By inducing DELTA family NOTCH ligands, RAS/MAPK signaling creates a positive feedback loop that represses HIF-1 and NHR-57 expression in the proximal VPCs and keeps them capable of differentiating. This regulatory network formed by the NOTCH, hypoxia, and RAS/MAPK pathways may allow the animals to adapt developmental processes to variations in oxygen concentration.
Volume 2(3)
Published 2019-6-1
DOI 10.26508/lsa.201800255
PII 2/3/e201800255
PMID 31126994
PMC PMC6536719
MeSH Alternative Splicing Animals Biomarkers Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Gain of Function Mutation Gene Expression Regulation Hypoxia / metabolism* Mitogen-Activated Protein Kinases / metabolism* Models, Biological Phenotype Protein Binding Proto-Oncogene Proteins p21(ras) / genetics Proto-Oncogene Proteins p21(ras) / metabolism* Receptors, Notch / metabolism Signal Transduction* Transcription Factors / genetics Transcription Factors / metabolism
IF 2.622
Times Cited 2
C.elegans tm4533