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Science. 2011 Jul 15;333(6040):342-345. doi: 10.1126/science.1204831.

Control of mitotic spindle angle by the RAS-regulated ERK1/2 pathway determines lung tube shape.

Author information

1
Department of Anatomy, University of California, San Francisco, CA 94158, USA.
2
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
3
Cancer Research Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
#
Contributed equally

Abstract

During early lung development, airway tubes change shape. Tube length increases more than circumference as a large proportion of lung epithelial cells divide parallel to the airway longitudinal axis. We show that this bias is lost in mutants with increased extracellular signal-regulated kinase 1 (ERK1) and ERK2 activity, revealing a link between the ERK1/2 signaling pathway and the control of mitotic spindle orientation. Using a mathematical model, we demonstrate that change in airway shape can occur as a function of spindle angle distribution determined by ERK1/2 signaling, independent of effects on cell proliferation or cell size and shape. We identify sprouty genes, which encode negative regulators of fibroblast growth factor 10 (FGF10)-mediated RAS-regulated ERK1/2 signaling, as essential for controlling airway shape change during development through an effect on mitotic spindle orientation.

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PMID:
21764747
PMCID:
PMC4260627
DOI:
10.1126/science.1204831
[Indexed for MEDLINE]
Free PMC Article

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