Toll receptors remodel epithelia by directing planar-polarized Src and PI3K activity

Dev Cell. 2021 Jun 7;56(11):1589-1602.e9. doi: 10.1016/j.devcel.2021.04.012. Epub 2021 Apr 30.


Toll-like receptors are essential for animal development and survival, with conserved roles in innate immunity, tissue patterning, and cell behavior. The mechanisms by which Toll receptors signal to the nucleus are well characterized, but how Toll receptors generate rapid, localized signals at the cell membrane to produce acute changes in cell polarity and behavior is not known. We show that Drosophila Toll receptors direct epithelial convergent extension by inducing planar-polarized patterns of Src and PI3-kinase (PI3K) activity. Toll receptors target Src activity to specific sites at the membrane, and Src recruits PI3K to the Toll-2 complex through tyrosine phosphorylation of the Toll-2 cytoplasmic domain. Reducing Src or PI3K activity disrupts planar-polarized myosin assembly, cell intercalation, and convergent extension, whereas constitutive Src activity promotes ectopic PI3K and myosin cortical localization. These results demonstrate that Toll receptors direct cell polarity and behavior by locally mobilizing Src and PI3K activity.

Keywords: Drosophila; PI3-kinase; Src; Toll-like receptor; actomyosin contractility; convergent extension; epithelial morphogenesis; planar polarity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / metabolism
  • Animals
  • Cell Membrane / genetics
  • Cell Polarity / genetics
  • Drosophila Proteins / genetics
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Embryonic Development / genetics*
  • Morphogenesis / genetics
  • Phosphatidylinositol 3-Kinases / genetics*
  • Toll-Like Receptors / genetics*
  • src-Family Kinases / genetics*


  • Drosophila Proteins
  • Toll-Like Receptors
  • Actomyosin
  • src-Family Kinases