RRC ID 53414
Author Luo S, Horvitz HR.
Title The CDK8 Complex and Proneural Proteins Together Drive Neurogenesis from a Mesodermal Lineage.
Journal Curr Biol
Abstract 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.
Volume 27(5)
Pages 661-672
Published 2017-3-6
DOI 10.1016/j.cub.2017.01.056
PII S0960-9822(17)30091-X
PMID 28238659
PMC PMC5384724
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / genetics* Basic Helix-Loop-Helix Transcription Factors / metabolism Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cyclin-Dependent Kinase 8 / genetics* Cyclin-Dependent Kinase 8 / metabolism Gene Expression Regulation, Developmental* Mesoderm / embryology Neurogenesis / genetics*
IF 9.601
Times Cited 3
C.elegans tm1238 tm3740 tm1768 tm1688 tm299 tm604 tm2279 tm1824 tm3105