The hypoxia-response pathway modulates RAS/MAPK-mediated cell fate decisions in Caenorhabditis elegans

Animals need to adjust many cellular functions to oxygen availability to adapt to changing environmental conditions. We have used the nematode as a model to investigate how variations in oxygen concentrations affect cell fate specification during development. Here, we show that several processes con...

Full description

Saved in:

Bibliographic Details
Published in:	Life science alliance Vol. 2; no. 3; p. e201800255
Main Authors:	Maxeiner, Sabrina, Grolleman, Judith, Schmid, Tobias, Kammenga, Jan, Hajnal, Alex
Format:	Journal Article
Language:	English
Published:	United States Life Science Alliance LLC 01-06-2019
Subjects:	Alternative Splicing Animals Biomarkers Caenorhabditis elegans - genetics Caenorhabditis elegans - metabolism Caenorhabditis elegans Proteins - genetics Caenorhabditis elegans Proteins - metabolism EPS Gain of Function Mutation Gene Expression Regulation Hypoxia - metabolism Laboratorium voor Nematologie Laboratory of Nematology Mitogen-Activated Protein Kinases - metabolism Models, Biological PE&RC 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
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Animals need to adjust many cellular functions to oxygen availability to adapt to changing environmental conditions. We have used the nematode 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Judith Grolleman’s present address is Radboud University Nijmegen Medical Centre, Department of Human Genetics, Nijmegen, The Netherlands
ISSN:	2575-1077 2575-1077
DOI:	10.26508/lsa.201800255