On shape and form

A classic epithelial movement involves the spreading of the edge of an epithelial sheet over a substrate. Such movements occur in the development of many animal phyla (where they are generally called ‘epiboly’) and during wound healing 3xParallels between wound repair and morphogenesis in the embryo. Grose, R. and Martin, P. Semin. Cell Dev. Biol. 1999; 10: 395–404Crossref | PubMed | Scopus (27)See all References3. Molecular-genetic analyses of such movements are rapidly elucidating the mechanisms by which epithelia spread. A central question in such movements concerns the origin of motile forces: what drives the epidermis to close? A simple example of epiboly occurs during Drosophila embryogenesis, when the epidermis spreads over amnioserosal cells towards the dorsal midline. This ‘dorsal closure’ movement has been the object of both embryological and genetic analyses in several labs. The presence of actin bundles at the leading edge of the advancing epithelium has led to the model of a ‘supracellular purse-string’ mechanism in which the hole is closed by contraction of the actin ring.Dan Kiehart (Duke University, USA) described tests of this hypothesis using time-lapse microscopy of dorsal closure in which cells or their actin cytoskeletons are labeled with green-fluorescent protein (GFP). Such work suggests that although contraction of an actin purse-string could account for some aspects of closure movements, additional unidentified forces in the epidermis and the substrate (amnioserosa cells) are also crucial. Paul Martin (University College, London, UK) showed striking movies of dorsal closure, in which leading cells (labeled with actin–GFP) could be seen extending filopodia and apparently ‘sampling’ the opposing face as a prelude to sealing up the dorsal midline 4xDynamic actin-based epithelial adhesion and cell matching during Drosophila dorsal closure. Jacinto, A. et al. Curr. Biol. 2000; 10: 1420–1426Abstract | Full Text | Full Text PDF | PubMed | Scopus (207)See all References4.Time-lapse movies of a different epiboly movement, ventral enclosure of the epidermis in Caenorhabditis elegans, were shown by Jeff Hardin (University of Wisconsin, Madison, USA), who emphasized the role of cadherin-mediated adhesion in the rapid sealing of the epithelium after closure. In C. elegans, neuronal substrate cells can also provide cues for epithelial migrations. Mutations in the neuronally expressed Eph receptor tyrosine kinase VAB-1 or its ephrin ligands disrupt epidermal morphogenesis (Andrew Chisholm, University of California, Santa Cruz, USA). The primary defects in such Eph signaling mutants appear to be a lack of adhesion between neuroblasts at an early stage in development, leading to disorganization of the substrate for epidermal movements.It is of intense interest to know whether such developmental epiboly movements share molecular mechanisms with wound healing. This can be addressed directly in Drosophila by wounding fly epithelia in wild-type and (for example) dorsal-closure mutant animals. Additionally, proteins involved in dorsal closure can be examined in wound healing situations. JNK signaling is normally activated, by unknown signals, in leading-edge cells during dorsal closure. Paul Martin reported that the JNK pathway is similarly activated in epithelial cells at the edge of wounds, suggesting that embryonic epiboly movements might indeed resemble ‘natural wounds’. Molecular genetic analysis of both natural and ‘induced’ closure movements is proceeding apace and should soon elucidate their similarities and differences. Although morphogenesis is to some extent a ‘last frontier’ of developmental biology, genetic analysis is rapidly making inroads on this terra incognita.