Wound healing recapitulates morphogenesis in Drosophila embryos

Abstract

The capacity to repair a wound is a fundamental survival mechanism that is activated at any site of damage throughout embryonic and adult life. To study the cell biology and genetics of this process, we have developed a wounding model in Drosophila melanogaster embryos that allows live imaging of rearrangements and changes in cell shape, and of the cytoskeletal machinery that draws closed an in vivo wound. Using embryos expressing green fluorescent protein (GFP) fusion proteins, we show that two cytoskeletal-dependent elements -- an actin cable and dynamic filopodial/lamellipodial protrusions -- are expressed by epithelial cells at the wound edge and are pivotal for repair. Modulating the activities of the small GTPases Rho and Cdc42 demonstrates that these actin-dependent elements have differing cellular functions, but that either alone can drive wound closure. The actin cable operates as a 'purse-string' to draw the hole closed, whereas filopodia are essential for the final 'knitting' together of epithelial cells at the end of repair. Our data suggest a more complex model for epithelial repair than previously envisaged and highlight remarkable similarities with the well-characterized morphogenetic movement of dorsal closure in Drosophila.

Rho GTPase activity zones and transient contractile arrays

“…(3) Zones are mobile and move in concert with the actomyosin array that they control. (4) Zones are semi-stable, such that they persist for as long as necessary to direct a particular actomyosin-dependent process and then disappear. The commonality of these dynamic features suggests that, while the details of zone generation and maintenance may differ, general regulatory principles are likely to operate in all cases.…”

“…Ref. 4). The Rho GTPases are targeted to membrane compartments by lipid modification and act in a switch-like manner, such that, in their active (GTP-bound) state, they bind to specific effector proteins that modulate different aspects of actin cytoskeleton function.…”

Apical and lateral cell protrusions interconnect epithelial cells in live Drosophila wing imaginal discs

“…Important cellular processes involve cell protrusions, including nutrient resorption (Louvard et al, 1992), mechanosensing (Frolenkov et al, 2004), photosensing (Corbeil et al, 2001;Pellikka et al, 2002), establishment of cell adhesion (Vasioukhin et al, 2000), cell migration (Fulga and Rorth, 2002), fusion of epithelial sheets (Jacinto et al, 2000;MartinBlanco et al, 2000), wound healing (Wood et al, 2002), axon guidance (Ritzenthaler et al, 2000), and cell-tocell communication (reviewed in Rorth, 2003). Intercellular communication is important for the growth and patterning of tissues and organs and cell protrusions may mediate this communication by one of several mechanisms.…”

Regulation of cell motile behavior by crosstalk between cadherin- and integrin-mediated adhesions

“…D uring development, cohesive tissues exhibit extensive rearrangements that range from en masse migration, such as in wound healing (1), to complex local cell rearrangements, such as cell intercalation (2). In extreme cases in development (3) and in diseases such as metastatic cancers (4), tissue cohesion is lost and single-cell migration enabled, which results in cells populating distant sites.…”