PMID- 29802149
OWN - NLM
STAT- MEDLINE
DCOM- 20180710
LR  - 20181114
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 145
IP  - 12
DP  - 2018 Jun 11
TI  - miR-133-mediated regulation of the Hedgehog pathway orchestrates embryo 
      myogenesis.
LID - 10.1242/dev.159657 [doi]
LID - dev159657
AB  - Skeletal myogenesis serves as a paradigm to investigate the molecular mechanisms 
      underlying exquisitely regulated cell fate decisions in developing embryos. The 
      evolutionarily conserved miR-133 family of microRNAs is expressed in the myogenic 
      lineage, but how it acts remains incompletely understood. Here, we performed 
      genome-wide differential transcriptomics of miR-133 knockdown (KD) embryonic 
      somites, the source of vertebrate skeletal muscle. These analyses, performed in 
      chick embryos, revealed extensive downregulation of Sonic hedgehog (Shh) pathway 
      components: patched receptors, Hedgehog interacting protein and the 
      transcriptional activator Gli1. By contrast, Gli3, a transcriptional repressor, 
      was de-repressed and confirmed as a direct miR-133 target. Phenotypically, 
      miR-133 KD impaired myotome formation and growth by disrupting proliferation, 
      extracellular matrix deposition and epithelialization. Together, these 
      observations suggest that miR-133-mediated Gli3 silencing is crucial for 
      embryonic myogenesis. Consistent with this idea, we found that activation of Shh 
      signalling by either purmorphamine, or KD of Gli3 by antisense morpholino, 
      rescued the miR-133 KD phenotype. Thus, we identify a novel Shh/myogenic 
      regulatory factor/miR-133/Gli3 axis that connects epithelial morphogenesis with 
      myogenic fate specification.
CI  - (c) 2018. Published by The Company of Biologists Ltd.
FAU - Mok, Gi Fay
AU  - Mok GF
AD  - School of Biological Sciences, Cell and Developmental Biology, University of East 
      Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
FAU - Lozano-Velasco, Estefania
AU  - Lozano-Velasco E
AD  - School of Biological Sciences, Cell and Developmental Biology, University of East 
      Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
FAU - Maniou, Eirini
AU  - Maniou E
AD  - School of Biological Sciences, Cell and Developmental Biology, University of East 
      Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
FAU - Viaut, Camille
AU  - Viaut C
AD  - School of Biological Sciences, Cell and Developmental Biology, University of East 
      Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
FAU - Moxon, Simon
AU  - Moxon S
AD  - The Earlham Institute, Norwich Research Park, Colney Lane, Norwich NR4 7UH, UK.
FAU - Wheeler, Grant
AU  - Wheeler G
AD  - School of Biological Sciences, Cell and Developmental Biology, University of East 
      Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
FAU - Munsterberg, Andrea
AU  - Munsterberg A
AUID- ORCID: 0000-0002-4577-4240
AD  - School of Biological Sciences, Cell and Developmental Biology, University of East 
      Anglia, Norwich Research Park, Norwich NR4 7TJ, UK a.munsterberg@uea.ac.uk.
LA  - eng
GR  - BB/K003437/Biotechnology and Biological Sciences Research Council/United Kingdom
GR  - BB/N007034/Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180611
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Carrier Proteins)
RN  - 0 (Gli3 protein, mouse)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Hhip protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (MicroRNAs)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Patched Receptors)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - 0 (Zinc Finger Protein Gli3)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/*biosynthesis
MH  - Cell Differentiation/genetics
MH  - Cell Proliferation/genetics
MH  - Chick Embryo
MH  - Down-Regulation
MH  - Gene Expression Regulation, Developmental
MH  - Gene Knockdown Techniques
MH  - Hedgehog Proteins/*metabolism
MH  - Membrane Glycoproteins/*biosynthesis
MH  - MicroRNAs/*genetics
MH  - Muscle Development/genetics/*physiology
MH  - Muscle, Skeletal/*embryology/growth & development
MH  - Nerve Tissue Proteins/*biosynthesis
MH  - Patched Receptors/*biosynthesis
MH  - Primary Cell Culture
MH  - Zinc Finger Protein GLI1/biosynthesis
MH  - Zinc Finger Protein Gli3/*biosynthesis
PMC - PMC6031409
OTO - NOTNLM
OT  - Basement membrane
OT  - Chick embryo
OT  - Gli3
OT  - Somite myogenesis
OT  - Sonic hedgehog signalling
OT  - miR-133
COIS- Competing interestsThe authors declare no competing or financial interests.
EDAT- 2018/05/29 06:00
MHDA- 2018/07/11 06:00
PMCR- 2018/06/11
CRDT- 2018/05/27 06:00
PHST- 2017/09/19 00:00 [received]
PHST- 2018/05/10 00:00 [accepted]
PHST- 2018/05/29 06:00 [pubmed]
PHST- 2018/07/11 06:00 [medline]
PHST- 2018/05/27 06:00 [entrez]
PHST- 2018/06/11 00:00 [pmc-release]
AID - dev.159657 [pii]
AID - DEV159657 [pii]
AID - 10.1242/dev.159657 [doi]
PST - epublish
SO  - Development. 2018 Jun 11;145(12):dev159657. doi: 10.1242/dev.159657.