The C. elegans CDK8 Mediator module regulates axon guidance decisions in the ventral nerve cord and during dorsal

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Visualizing Neuroblast Cytokinesis During C. elegans Embryogenesis
09:52

Visualizing Neuroblast Cytokinesis During C. elegans Embryogenesis

Published on: March 12, 2014

Andreas Steimel1, Jinkyo Suh, Angela Hussainkhel

  • 1Department of Biological Sciences, Simon Fraser University, Burnaby, BC, Canada.

Developmental Biology
|March 6, 2013
PubMed

Insights

The Mediator

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Axon guidance relies on growth cone receptors detecting navigation cues.
  • Proper axon pathfinding depends on regulated receptor expression and activity.
  • The Mediator complex is crucial for gene transcription by RNA polymerase II.

Purpose of the Study:

  • To investigate the role of Mediator complex subunit LET-19/MDT-13 in axon guidance.
  • To identify specific Mediator components involved in neuronal navigation.
  • To elucidate the mechanism by which the CDK8 module regulates axon pathfinding.

Main Methods:

  • Genetic screening for axon guidance mutants.
  • Analysis of Mediator complex subunit functions in neurons.
  • Gene expression profiling in interneurons.
  • Genetic interaction studies using mutations in let-19/mdt-13 and sax-3.

Main Results:

  • LET-19/MDT-13, a Mediator complex component, is essential for specific axon navigation decisions.
  • All subunits of the CDK8 module and some other Mediator components are required for axon guidance.
  • let-19/mdt-13 regulates a large number of genes in interneurons.
  • Mutation in sax-3 suppresses commissure navigation defects in cdk-8 mutants.

Conclusions:

  • The CDK8 module of the Mediator complex plays a critical role in axon guidance.
  • The CDK8 module appears to specifically repress the SAX-3/ROBO pathway.
  • This repression by the CDK8 module is necessary for proper commissure navigation.

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