Developmental Biology

Mechanical Control by Planar Cell Polarity

Science Signaling  15 May 2012:
Vol. 5, Issue 224, pp. ec137
DOI: 10.1126/scisignal.2003216

Planar cell polarity (PCP) pathways polarize cells across tissues to allow proper tissue morphogenesis and the development of polarized epithelial appendages such as bristles. In the fruit fly Drosophila melanogaster, PCP signaling through the atypical cadherin Fat induces asymmetric subcellular accumulation of the myosin Dachs, which influences cell growth and oriented cell division. Fat heterodimerizes with another atypical cadherin, Dachsous (Ds), and this binding requires phosphorylation of both cadherins’ extracellular domains by the Golgi-localized kinase Four-jointed (Fj). It has been unclear how this heterophilic interaction generates polarity, because Fat and Ds are uniformly distributed on cell membranes. Bosveld et al. report that, during morphogenesis of the Drosophila thorax, asymmetric distribution of fluorescently tagged Dachs was induced at the boundary between opposing gradients of ds and fj expression. Experimentally manipulating ds or fj expression patterns altered the area of Dachs asymmetry so that it always occurred at the boundary between opposing gradients. Cell membranes where Dachs accumulated were under more tension than cell membranes lacking Dachs, and modeling indicated that these differential tensions could be sufficient to account for the cell rearrangements that drive the contractions and morphogenesis of this tissue. Dachs accumulation correlated with cell rearrangements and tissue contraction but not with cell division rate or orientation, and reducing Dachs accumulation by RNA interference perturbed normal morphogenetic movements. The authors thus conclude that the planar polarized distribution of Dachs drives tissue morphogenesis by inducing asymmetric cellular contractions in domains defined by the intersection of Ds and Fj gradients. This model also offers an explanation for how tissue-level asymmetries can be translated into asymmetry at the cellular level.

F. Bosveld, I. Bonnet, B. Guirao, S. Tlili, Z. Wang, A. Petitalot, R. Marchand, P.-L. Bardet, P. Marcq, F. Graner, Y. Bellaïche, Mechanical control of morphogenesis by Fat/Dachsous/Four-jointed planar cell polarity pathway. Science 336, 724–727 (2012). [Abstract] [Full Text]