The CDK8 Complex and Proneural Proteins Together Drive Neurogenesis from a Mesodermal Lineage
Name
nihms848594.pdf
Size
1.04 MB
Format
Adobe PDF
Checksum (MD5)
7b3b33e81e3b7b7bf0d71214fb751016
Author(s)
Luo, Shuo
Horvitz, Howard Robert
Date Issued
February 2017
Journal
Current Biology
Publisher
Elsevier BV
Citation
Luo, Shuo, and H. Robert Horvitz. “The CDK8 Complex and Proneural Proteins Together Drive Neurogenesis from a Mesodermal Lineage.” Current Biology 27, no. 5 (March 2017): 661–672.
Version
Author's final manuscript
Abstract
© 2017 Elsevier Ltd At least some animal species can generate neurons from mesoderm or endoderm, but the underlying mechanisms remain unknown. We screened for C. elegans mutants in which the presumptive mesoderm-derived I4 neuron adopts a muscle-like cell fate. From this screen, we identified HLH-3, the C. elegans homolog of a mammalian proneural protein (Ascl1) used for in vitro neuronal reprogramming, as required for efficient I4 neurogenesis. We discovered that the CDK-8 Mediator kinase module acts together with a second proneural protein, HLH-2, and in parallel to HLH-3 to promote I4 neurogenesis. Genetic analysis revealed that CDK-8 most likely promotes I4 neurogenesis by inhibiting the CDK-7/CYH-1 (CDK7/cyclin H) kinase module of the transcription initiation factor TFIIH. Ectopic expression of HLH-2 and HLH-3 together promoted expression of neuronal features in non-neuronal cells. These findings reveal that the Mediator CDK8 kinase module can promote non-ectodermal neurogenesis and suggest that inhibiting CDK7/cyclin H might similarly promote neurogenesis.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CUB.2017.01.056
