Regulation of lung endoderm progenitor cell behavior by miR302/367

Development. 2011 Apr;138(7):1235-45. doi: 10.1242/dev.061762. Epub 2011 Feb 24.


The temporal and spatial control of organ-specific endoderm progenitor development is poorly understood. miRNAs affect cell function by regulating programmatic changes in protein expression levels. We show that the miR302/367 cluster is a target of the transcription factor Gata6 in mouse lung endoderm and regulates multiple aspects of early lung endoderm progenitor development. miR302/367 is expressed at early stages of lung development, but its levels decline rapidly as development proceeds. Gain- and loss-of-function studies show that altering miR302/367 expression disrupts the balance of lung endoderm progenitor proliferation and differentiation, as well as apical-basal polarity. Increased miR302/367 expression results in the formation of an undifferentiated multi-layered lung endoderm, whereas loss of miR302/367 activity results in decreased proliferation and enhanced lung endoderm differentiation. miR302/367 coordinates the balance between proliferation and differentiation, in part, through direct regulation of Rbl2 and Cdkn1a, whereas apical-basal polarity is controlled by regulation of Tiam1 and Lis1. Thus, miR302/367 directs lung endoderm development by coordinating multiple aspects of progenitor cell behavior, including proliferation, differentiation and apical-basal polarity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • Endoderm / cytology*
  • Endoderm / metabolism
  • GATA6 Transcription Factor / genetics
  • GATA6 Transcription Factor / metabolism*
  • Gene Expression Regulation, Developmental
  • Lung / cytology*
  • Lung / embryology
  • Lung / metabolism
  • Mice
  • Mice, Transgenic
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / metabolism*


  • GATA6 Transcription Factor
  • Gata6 protein, mouse
  • MicroRNAs