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  current news   Press   selected story    
     
  9th September 2011  
 

Prdm1a and miR-499 act sequentially to restrict Sox6 activity to the fast-twitch muscle lineage in the zebrafish embryo

 
 




Authors
XinGang WANG1, Yosuke ONO1, Swee Chuan TAN1, Ruth Jin Fen CHAI1,4, Caroline PARKIN1,3, Philip W INGHAM1,2.

1 - Institute of Molecular and Cell Biology, Singapore.
2 - Department of Biological Sciences, National University of Singapore.
3 - MRC Centre for Developmental and Biomedical Genetics, Firth Court, Western Bank, Sheffield, S10       2TN, UK
4 - School of Anatomy and Human Biology, The University of Western Australia, Perth 6009, WA,       Australia

Published in Development, 31 August 2011 (Epub ahead of print.)

Abstract
Sox6 has been proposed to play a conserved role in vertebrate skeletal muscle fibre-type specification. In zebrafish, sox6 transcription is repressed in slow-twitch progenitors by the Prdm1a transcription factor. Here we identify sox6 cis-regulatory sequences that drive fast-twitch-specific expression in a Prdm1a–dependent manner. We show that sox6 transcription subsequently becomes derepressed in slow-twitch fibres whereas Sox6 protein remains restricted to fast-twitch fibres. We find that translational repression of sox6 is mediated by miR-499, the slow-twitch-specific expression of which is in turn controlled by Prdm 1a, forming a regulatory loop that initiates and maintains the slow-twitch muscle lineage.

 
 

 
 


Figure Legend : Derepression of sox6 transcription but not translation in slow-twitch fibres (A-C) Optical saggital sections of posterior trunk region of Tg(5.7kb sox6:EGFP)i253; Tg(9.7kb smyhc1:lyn-tdTomato)i261 larvae. At 2 dpf (A), EGFP expression is restricted exclusively to fast-twitch fibres (green) lying beneath the superficial slow-twitch fibres (red). At 4dpf (B), EGFP expression is detectable in a few slow-twitch fibres (arrowheads). By 6 dpf (C) all slow-twitch fibres express EGFP. Transverse cryostat sections of Tg(BACsmyhc1:GFP)i108 (D,F) or Tg(9.7kb smyhc1:lyntdTomato)i261 (E,G) embryos/larvae hybridised with probe for sox6 mRNA (red) or stained with anti-Sox6 antibody (green) respectively. (H-K) Transverse cryostat sections of 6 dpf larvae carrying 5.7 kb sox6:EGFP reporter constructs with differing 3’UTRs, shown schematically in (L). (H) Expression of EGFP driven by the 5.7 kb reporter construct with the SV40 3’UTR in slow-twitch fibres, identified by mABF59 staining (red) is repressed by replacement of the SV40 3’UTR with the endogenous sox6 3’UTR (I). Mutation (J) or deletion (K) of the five putative miR-499 target sites restores ectopic EFGP expression in slow-twitch fibres. Note the increased levels of expression caused by deletion of the miR-499 sites (K).

For more information on Philip INGHAM’s laboratory, please click here