At first glance, the mammalian epidermis seems very different from that of flies ( Fig. 1A ), but there are striking parallels with respect to the formation and maintenance of epithelial barriers in the two species, illustrating a probable common ancestral origin. For example, claudin-family proteins forming the tight junctions between epithelial cells seem to have similar functions in both flies (Behr et al., 2003; Nelson et al., 2010; Wu et al., 2004) and mice (Furuse et al., 2002) [see the 2009 article by Furuse for a review on the role of claudins and other tight junction proteins in mammalian epithelia (Furuse, 2009) ]. Similarly, the transcription factor Grainyhead (Grh) plays an important role in regulating the expression of genes that are required to form the cross-linked outer epidermal surface both in flies (Bray and Kafatos, 1991) and mice (Matsuki et al., 1998; Ting et al., 2005) (although the set of Grh target genes seems to be different in each species). Grh also regulates genes that are involved in wound repair both in flies (Mace et al., 2005) and mice (Ting et al., 2005) .