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04.04.16 Rawlins lab identify an active signalling mechanism that maintains quiescence in the airway epithelium

last modified Apr 06, 2016 04:34 PM
New paper in Developmental Cell from the Rawlins lab shows that active signalling via FGFR1 is required to maintain steady-state cell turnover in airway epithelium
04.04.16 Rawlins lab identify an active signalling mechanism that maintains quiescence in the airway epithelium

Graphical abstract from the paper

An FGFR1-SPRY2 Signaling Axis Limits Basal Cell Proliferation in the Steady-State Airway Epithelium

Balasooriya GI, Johnson JA, Basson MA, Rawlins EL (2016) Developmental Cell 37(1): 85-97

doi: 10.1016/j.devcel.2016.03.001.

 

Highlights and summary from the paper:

  • FGFR1 signaling is important for inhibiting airway stem cell proliferation
  • FGFR1 post-translationally activates SPRY2, which inhibits activity of other Receptor Tyrosine Kinases (RTKs)
  • Balancing the activity of different RTKs tunes airway stem cell proliferation rates
  • Ciliated cell fate specification also requires FGFR1 but does not require SPRY2

Summary

The steady-state airway epithelium has a low rate of stem cell turnover but can nevertheless mount a rapid proliferative response following injury. This suggests a mechanism to restrain proliferation at steady state. One such mechanism has been identified in skeletal muscle in which pro-proliferative FGFR1 signaling is antagonized by SPRY1 to maintain satellite cell quiescence.

Surprisingly, we found that deletion of Fgfr1 or Spry2 in basal cells of the adult mouse trachea caused an increase in steady-state proliferation. We show that in airway basal cells, SPRY2 is post-translationally modified in response to FGFR1 signaling. This allows SPRY2 to inhibit intracellular signaling downstream of other receptor tyrosine kinases and restrain basal cell proliferation.

An FGFR1-SPRY2 signaling axis has previously been characterized in cell lines in vitro. We now demonstrate an in vivo biological function of this interaction and thus identify an active signaling mechanism that maintains quiescence in the airway epithelium.

 

Reproduced under Creative Commons Attribution (CC BY 4.0)

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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