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

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.

SUBMITTER: Tang N

PROVIDER: S-EPMC4260627 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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

Tang Nan N Marshall Wallace F WF McMahon Martin M Metzger Ross J RJ Martin Gail R GR

Science (New York, N.Y.) 20110701 6040

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 ...[more]

PMID: 21764747

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