Regulation of lung endoderm progenitor cell behavior by miR302/367

Y Tian, Y Zhang, L Hurd, S Hannenhalli, F Liu… - …, 2011 - journals.biologists.com
Y Tian, Y Zhang, L Hurd, S Hannenhalli, F Liu, MM Lu, EE Morrisey
Development, 2011journals.biologists.com
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 …
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.
journals.biologists.com