title: The C. elegans CDK8 Mediator module regulates axon guidance decisions in the ventral nerve cord and during dorsal axon navigation.
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.
authors: Department of Biological Sciences, Simon Fraser University, Burnaby, BC, Canada.
authors: Andreas
authors: A
authors: Steimel
authors: Jinkyo
authors: J
authors: Suh
authors: Angela
authors: A
authors: Hussainkhel
authors: Samineh
authors: S
authors: Deheshi
authors: Jennifer M
authors: JM
authors: Grants
authors: Richard
authors: R
authors: Zapf
authors: Donald G
authors: DG
authors: Moerman
authors: Stefan
authors: S
authors: Taubert
authors: Harald
authors: H
authors: Hutter
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000196:embryology*; D002465:Cell Movement / Q000502:physiology*; D056850:Cyclin-Dependent Kinase 8 / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D020439:Growth Cones / Q000378:metabolism; D056892:Mediator Complex / Q000378:metabolism*; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009420:Nervous System / Q000196:embryology*; D034622:RNA Interference; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D056850:Cyclin-Dependent Kinase 8; D017931:DNA Primers; D056892:Mediator Complex; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins