MicroRNA-30a regulates zebrafish myogenesis through targeting the transcription factor Six1
- O'Brien, J.H., Hernandez-Lagunas, L., Artinger, K.B., Ford, H.L.
- Journal of Cell Science 127(Pt 10): 2291-301 (Journal)
- Registered Authors
- Artinger, Kristin Bruk
- microRNA-30a, Myogenesis, Six1, Zebrafish
- MeSH Terms
- Cell Differentiation/physiology
- Cell Proliferation/physiology
- Gene Expression Regulation, Developmental
- Gene Knockdown Techniques
- Gene Regulatory Networks
- Homeodomain Proteins/biosynthesis
- Homeodomain Proteins/genetics*
- Homeodomain Proteins/metabolism*
- Muscle Development/physiology*
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism*
- 24634509 Full text @ J. Cell Sci.
O'Brien, J.H., Hernandez-Lagunas, L., Artinger, K.B., Ford, H.L. (2014) MicroRNA-30a regulates zebrafish myogenesis through targeting the transcription factor Six1. Journal of Cell Science. 127(Pt 10):2291-301.
Precise spatiotemporal regulation of the SIX1 homeoprotein is required to coordinate vital tissue development, including myogenesis. While SIX1 is downregulated in most tissues following embryogenesis, it is re-expressed in numerous cancers, including tumors derived from muscle progenitors. Despite critical roles in development and disease, upstream regulation of SIX1 expression has remained elusive. Here we identify the first direct mechanism for Six1 regulation in embryogenesis, through microRNA30a (miR30a)-mediated repression. In zebrafish somites, we show that miR30a and six1a/b are expressed in an inverse temporal pattern. Overexpression of miR30a leads to a reduction in six1a/b levels, and results in increased apoptosis and altered somite morphology, which phenocopies six1a/b knockdown. Conversely, miR30a inhibition leads to increased Six1 expression and abnormal somite morphology, revealing a role for endogenous miR30a as a myomiR. Importantly, restoration of six1a in miR30a-overexpressing embryos restores proper myogenesis. These data demonstrate a novel role for miR30a at a key node in the myogenic regulatory gene network through controlling Six1 expression.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes