RRC ID 46204
Author Steimel A, Suh J, Hussainkhel A, Deheshi S, Grants JM, Zapf R, Moerman DG, Taubert S, Hutter H.
Title The C. elegans CDK8 Mediator module regulates axon guidance decisions in the ventral nerve cord and during dorsal axon navigation.
Journal Dev Biol
Abstract Receptors expressed on the growth cone of outgrowing axons detect cues required for proper navigation. The pathway choices available to an axon are in part defined by the set of guidance receptors present on the growth cone. Regulated expression of receptors and genes controlling the localization and activity of receptors ensures that axons respond only to guidance cues relevant for reaching their targets. In genetic screens for axon guidance mutants, we isolated an allele of let-19/mdt-13, a component of the Mediator, a large ~30 subunit protein complex essential for gene transcription by RNA polymerase II. LET-19/MDT-13 is part of the CDK8 module of the Mediator. By testing other Mediator components, we found that all subunits of the CDK8 module as well as some other Mediator components are required for specific axon navigation decisions in a subset of neurons. Expression profiling demonstrated that let-19/mdt-13 regulates the expression of a large number of genes in interneurons. A mutation in the sax-3 gene, encoding a receptor for the repulsive guidance cue SLT-1, suppresses the commissure navigation defects found in cdk-8 mutants. This suggests that the CDK8 module specifically represses the SAX-3/ROBO pathway to ensure proper commissure navigation.
Volume 377(2)
Pages 385-98
Published 2013-5-15
DOI 10.1016/j.ydbio.2013.02.009
PII S0012-1606(13)00101-2
PMID 23458898
MeSH Animals Axons / physiology* Caenorhabditis elegans / embryology* Cell Movement / physiology* Cyclin-Dependent Kinase 8 / metabolism* DNA Primers / genetics Gene Expression Profiling Gene Expression Regulation, Developmental Growth Cones / metabolism Mediator Complex / metabolism* Microscopy, Confocal Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism Nervous System / embryology* RNA Interference Receptors, Immunologic / genetics Receptors, Immunologic / metabolism Roundabout Proteins
IF 2.896
Times Cited 8
C.elegans tm1238 tm1704 tm3740 tm2182 tm2893