First Author | Tang N | Year | 2011 |
Journal | Science | Volume | 333 |
Issue | 6040 | Pages | 342-345 |
PubMed ID | 21764747 | Mgi Jnum | J:174194 |
Mgi Id | MGI:5052190 | Doi | 10.1126/science.1204831 |
Citation | Tang N, et al. (2011) Control of mitotic spindle angle by the RAS-regulated ERK1/2 pathway determines lung tube shape. Science 333(6040):342-5 |
abstractText | 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. |