Research Groups

Cell Mechanics

Anyone who watches a movie of a developing embryo is immediately struck by the dramatic choreography of tissue movements and shape changes, and appreciates intuitively that growth and morphogenesis depend on organized physical forces exerted by cells.  Epithelial cells, like those in mesenchymal tissues, can sense and exert forces where they contact the extracellular matrix.  They can also sense and exert forces cells on each other through their apico-lateral contacts. How do epithelial cells polarize their force generating machinery and remodel their contacts to drive oriented tissue growth and morphogenesis? We are exploring these questions in the developing wing of Drosophila using genetic and biophysical approaches, along with quantitative image analysis and modelling.

Most of the growth of the future wing occurs in larvae (Figure 1A).  At this stage, the wing epithelium is called a wing imaginal disc, and consists of a folded epithelial sac with an apical lumen.  Although the shape of the wing is unrecognizable, morphogen signalling systems present at lineage restriction boundaries are already controlling growth, and generating patterns of gene expression that will later specify the position of wing veins and sensory organs.  When larvae have reached a critical size, they stop feeding and pupariate.  At this time, the wing imaginal disc begins to undergo dramatic morphogenetic movements that sculpt the wing into its adult shape.  These occur in two different phases. First, the larval wing epithelium essentially turns itself inside out – changing from an epithelial sac with an apical lumen to an epithelial bilayer whose basal sides are opposed to each other (Figure 1B).  

This process, called wing eversion, produces a crude approximation of the adult wing shape and ends as wing epithelial cells secrete a temporary cuticle from their apical surface (Figure 1C).

The second phase of morphogenesis, called hinge contraction/elongation, begins with the shedding of the temporary cuticle throughout most of the wing (Figure 1C,D).  As the cuticle is released, patterned contractions shape the wing hinge and reduce its area.  These contractions generate anisotropic tension along the proximal-distal (PD) axis of the adjacent wing blade because it remains connected to the overlying cuticle at its edge.  This produces anisotropic tissue flows that elongate the wing in the PD axis and narrow it in the anterior-posterior (AP) axis. During these flows, wing epithelial cells divide, change shape and exchange neighbours (Aigouy et al., 2010).  They also regularize their packing geometry to form an array of hexagons (Classen et al., 2005). 

Merkel, M., Sagner, A., Gruber, F., Etournay, R., Blasse, C., Myers, E., Eaton, S*. and Jülicher, F. The Balance of Prickle/Spiny-Legs isoforms controls the amount of coupling between Core and Fat PCP systems (2014) Current Biology 24:2111-2123

Umetsu, D., Aigouy, B., Aliee, M. Sui, L. Eaton, S. Jülicher, F., and Dahmann, C. (2014) Local increases in mechanical tension shape compartment boundaries by biasing cell intercalations. Current Biology 24:1798-1805

Sagner, A., Merkel, M., Aigouy, B., Jülicher, F. and Eaton, S.*  Establishment of global patterns of planar polarity during growth of the Drosophila wing epithelium. (2012) Current Biology 22:1-6

Staple D, Farhadifar R, Röper J, Aigouy B, Eaton S, Jülicher J. (2010). Mechanics and remodeling of cell packings in epithelia.  Eur.Phys. J. 33: 117-127

Aigouy B, Farhadifar R, Staple DB, Sagner A, Röper JC, Jülicher F, Eaton S.* (2010). Cell flow reorients the axis of planar polarity in the wing epithelium of Drosophila. Cell 142, 773-86.

Mottola G, Classen AK, González-Gaitán M, Eaton S, Zerial M. (2010). A novel function for the Rab5 effector Rabenosyn-5 in planar cell polarity. Development. 137, 2353-64. 

Fernandez-Gonzalez R, Simoes Sde M, Röper JC, Eaton S, Zallen JA. (2009). Myosin II dynamics are regulated by tension in intercalating cells. Dev Cell. 17, 736-43. 

Farhadifar, R., Roper, J. C., Aigouy, B., Eaton, S*., and Jülicher, F*. (2007). The Influence of Cell Mechanics, Cell-Cell Interactions, and Proliferation on Epithelial Packing. Curr Biol 17, 2095-2104. 

Classen, A., Anderson, K., Marois, E., and Eaton, S*. (2005). Hexagonal Packing of Drosophila Wing Epithelial Cells by the Planar Cell Polarity Pathway. Dev Cell 9, 805-817. 

Das G, Jenny A, Klein TJ, Eaton S, Mlodzik M. (2004). Diego interacts with Prickle and Strabismus/Van Gogh to localize planar cell polarity complexes. Development 131, 4467-76 

Hannus, M., Feiguin, F., Heisenberg, C. P., and Eaton, S*. (2002). Planar cell polarization requires Widerborst, a B' regulatory subunit of protein phosphatase 2A. Development 129, 3493-3503. 

Feiguin, F., Hannus, M., Mlodzik, M., and Eaton, S*. (2001). The ankyrin repeat protein Diego mediates Frizzled-dependent planar polarization. Dev Cell 1, 93-101 

Paricio, N., Feiguin, F., Boutros, M., Eaton, S., and Mlodzik, M. (1999). The Drosophila STE-20-like kinase Misshapen is required downstream of the Frizzled receptor in planar polarity signaling. EMBO J 18, 4669-4678.