RRC ID |
46204
|
著者 |
Steimel A, Suh J, Hussainkhel A, Deheshi S, Grants JM, Zapf R, Moerman DG, Taubert S, Hutter H.
|
タイトル |
The C. elegans CDK8 Mediator module regulates axon guidance decisions in the ventral nerve cord and during dorsal axon navigation.
|
ジャーナル |
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.
|
巻・号 |
377(2)
|
ページ |
385-98
|
公開日 |
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
|
IF |
2.896
|
引用数 |
8
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
|
リソース情報 |
線虫 |
tm1238
tm1704
tm3740
tm2182
tm2893 |