Parallels between tissue repair and embryo morphogenesis

Abstract

Review 3022tissue movements as in the adult, although on a much smaller scale, but only at late foetal stages is healing accompanied by an inflammatory response (Hopkinson-Woolley et al., 1994; Cowin et al., 1998). Prior to these stages, inflammation is absent and the embryo is capable of essentially perfect, near regenerative repair, with no resulting scar. Wound healing, even in the embryo (Fig. 2), is a complex process involving the coordination of several cell behaviours from several different cell types, and for each stage of wound repair there are fundamental cell biology issues that still need resolving (see Box 1). Developmental models of wound healingA number of naturally occurring morphogenetic events involve tissue movements similar to those required for wound healing. Two of the clearest of these, both of which involve closure of epithelial holes, are dorsal closure in the Drosophila embryo and C. elegans ventral enclosure. Dorsal closure in DrosophilaNear the end of the complex and intricately orchestrated cell and tissue movements of Drosophila gastrulation, including the extension of the germband over the dorsal surface and its subsequent retraction, a large hole is left behind on the dorsal surface of the embryo. An extra-embryonic membrane consisting of large flat cells -the amnioserosa -covers this dorsal hole (Fig. 3A-D). The process of bringing together the two epithelial edges over the amnioserosa to close the hole and form a seamless dorsal midline is known as dorsal closure. The dorsal hole is elliptical or eye shaped, and closure proceeds from the anterior and posterior ends (or canthi) of the opening towards the middle. The integrated efforts of three groups of cells are required for proper closure: the dorsalmost row of ectodermal cells defining the perimeter of the epithelial sheet, termed the leading edge (LE) cells; the more ventral epithelial (VE) cells; and the exposed amnioserosa (AS). Dorsal closure has been described as taking place in four phases (for detailed descriptions, see Harden, 2002;Jacinto et al., 2002b). The first phase, initiation (Fig. 3A), begins just prior to the completion of germband retraction, with the two opposing epithelial sheets moving slowly towards one another as a consequence of amnioserosal cell contraction. The trigger(s) required to start the dorsal closure process are not known, but probably include a combination of chemical and mechanical cues, including dorsoventral patterning information and mechanical stresses generated by germband retraction.During the second phase, epithelial sweeping ( Fig. 3B), leading edge cells accumulate actin and myosin just beneath the cell membrane at their dorsalmost (apical) edge. This Factin accumulation forms a contractile cable, which pulls the leading edges of the epithelial sheets taut (Jacinto et al., 2002a) Development 131 (13) Fig. 1. The cellular players in the healing of a skin wound. The wound is first 'plugged' with a fibrin clot, which is infiltrated by inflammatory cells, fibroblasts and a dense plexus...

Expression patterns of the lysophospholipid receptor genes during mouse early development

“…3A,B), indicating a regional heterogeneity of the eyelid anlagen by this stage or a functional difference of these two receptors in eyelid development. As reported previously, epithelial proliferation and subsequent migration leads to eyelid development (Martin and Parkhurst, 2004;Tao et al, 2005). Our findings suggest that LPA/S1P lipids might regulate epithelial migration in mouse eyelid development by binding to LPA 1 and S1P 1-3 receptors.…”

Emergent properties of neural repair: elemental biology to therapeutic concepts

“…Such similarity in tissue repair in stroke to neurodevelopment has prompted suggestions that brain regeneration recapitulates development 117. Similar comparisons to regeneration and development have been made in other systems, such as kidney, bone, liver, and skin 118, 119, 120, 121…”

Membrane dynamics of cleavage furrow closure in Xenopus laevis

“…Finally, that Xenopus embryos manage to seal furrows under a variety of experimental conditions, including expansion or removal of the vitelline envelope, indicates a robust and responsive system, presumably using redundant interacting regulatory pathways, and, therefore, reflecting the developmental importance of furrow closure. In this report, we examined two dynamic activities of furrow closure that are commonly encountered in other epithelial sheet fusions, namely the development of an actin-dependent purse-string constriction along free apical-basolateral margins, and a margin-associated protrusive activity (Martin and Parkhurst, 2004). Additionally, we found that the basolateral domains autonomously produce active protrusive zones that act across large surface areas to bring bare adhesive membranes into contact.…”

“…Zippering by the first cleavage furrow closes a 1-mm opening in approximately 15 min. While wound closure in tissue culture models (Farooqui and Fenteany, 2004) or Drosophila dorsal closure (Martin and Parkhurst, 2004) typically involves participation by hundreds of cells in multiple rows, Xenopus firstfurrow closure involves the suturing of apical-basolateral margins between only two blastomeres. Epithelial wound-healing models are essentially 2D, whereas Xenopus cleavage is 3D, with interactions between both the basolateral domains and the apical margins contributing to the closure process.…”