ZFIN ID: ZDB-PUB-120529-11
The smooth muscle microRNA miR-145 regulates gut epithelial development via a paracrine mechanism
Zeng, L., and Childs, S.J.
Date: 2012
Source: Developmental Biology   367(2): 178-186 (Journal)
Registered Authors: Childs, Sarah J., Zeng, Lei
Keywords: miR-145, epithelium, smooth muscle, Gata6, Klf5a, zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Bone Morphogenetic Protein 4/genetics
  • Bone Morphogenetic Protein 4/metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Digestive System/embryology
  • Digestive System/metabolism
  • GATA Transcription Factors/genetics
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Hedgehog Proteins/genetics
  • Hedgehog Proteins/metabolism
  • Kruppel-Like Transcription Factors/genetics
  • MicroRNAs/genetics*
  • Morpholinos/genetics
  • Muscle, Smooth/embryology
  • Muscle, Smooth/metabolism
  • Myoblasts, Smooth Muscle/cytology
  • Myoblasts, Smooth Muscle/metabolism
  • Myocytes, Smooth Muscle/cytology
  • Myocytes, Smooth Muscle/metabolism
  • Paracrine Communication
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 22609551 Full text @ Dev. Biol.

MicroRNAs are potent modulators of cellular differentiation. miR-145 is expressed in, and promotes the differentiation of vascular and visceral smooth muscle cells (SMCs). Interestingly, we have observed that miR-145 also promotes differentiation of the gut epithelium in the developing zebrafish, a cell type where it is not expressed. Here we identify that a paracrine pathway involving the morphogens Sonic hedgehog (Shh) in epithelium and bone morphogenic protein 4 (Bmp4) in SMCs is modulated by miR-145. We show that expression of miR-145 in visceral SMCs normally represses the expression of the morphogen bmp4, as loss of miR-145 leads to upregulation of bmp4 in SMCs. We show that bmp4 in turn controls expression of Shh in the visceral epithelium. Conversely, in miR-145 morphants where bmp4 expression is increased, expression of sonic hedgehog a (shha) is strongly increased in gut epithelium. We show that expression of bmp4 is modulated by the miR-145 direct target gata6 but not a second potential direct target, klf5a. Thus although miR-145 is a tissue-restricted microRNA, it plays an essential role in promoting the patterning of both gut layers during gut development via a paracrine mechanism.