www.landesbioscience.com Fly 327 Fly 5:4, 327-332; October/November/December 2011; © 2011 Landes Bioscience EXTRA VIEW EXTRA VIEW Extra View to: Gettings M, Serman F, Rousset R, Bagnerini P, Almeida L, Noselli S. JNK signalling controls remodelling of the segment boundary through cell reprogramming during Drosophila morphogenesis. PLoS Biol 2010; 8:e1000390; 20543996; http://dx.doi.org/10.1371/journal. pbio.1000390 Keywords: development, morphogenesis, regeneration, dorsal closure, cell plastic- ity, reprogramming, transdifferentiation, JNK, segment boundary, selector gene Abbreviations: JNK, Jun N-terminal Kinase; M, mixer cell; M*, Mixer Cell mirror image; S, segment boundary; PS, parasegment boundary; Wg, Wingless; En, Engrailed; PcG, Polycomb Group; Dpp, Decapentaplegic; TGF b, Tumor Growth Factor b Submitted: 03/23/11 Revised: 05/04/11 Accepted: 05/05/11 http://dx.doi.org/10.4161/fly.5.4.16354 *Correspondence to: Stéphane Noselli; Email: noselli@unice.fr W hat triggers a differentiated cell to naturally change its cell fate? Cell reprogramming is a rare and intriguing phenomenon from a develop- mental point of view. It has been mostly involved in boundary sharpening dur- ing development, tissue regeneration and cancer. Developmental models of the understanding of pathology-related cell reprogramming are yet to be estab- lished. Here we comment on the recently discovered “Mixer Cells” undergoing highly stereotyped developmental repro- gramming during Drosophila epider- mal morphogenesis. The JNK signaling pathway, which is involved in regenera- tive cell reprogramming, is essential to Mixer Cell formation. Thus the Mixer Cell model may provide a link between developmental cell reprogramming and regeneration. Introduction Reprogramming of differentiated cells or ‘metaplasia’ or ‘transdifferentiation,’ is a process by which differentiated cells switch their identity to a different cell type. 1,2 This involves de novo expression of lineage-spe- cific selector genes that are important for cell identity specification. Reprogramming is amongst nature’s clever regenerative strategies. It is involved in the hydrozoan Turritopsis nutriculata’s never-ending life cycle, 3 Drosophila disc transdetermina- tion, 4 amphibian lens regeneration, 5 zebraf- ish and avian inner-hair cell regeneration 6,7 and as recently shown, in insulin-producing beta pancreatic cell regeneration in adult Mixer Cell formation during dorsal closure A new developmental model of JNK-dependent natural cell reprogramming in Drosophila Melanie Gettings 1,2 and Stéphane Noselli 1, * 1 Institute of Developmental Biology and Cancer-IBDC-Nice; University of Nice Sophia Antipolis; CNRS UMR 6543; Nice, France; 2 LBCMCP; Université Paul Sabatier; CNRS UMR 5088; Toulouse, France mice. 8 In humans, metaplasia is linked to cancer. In this case, misregulated transdif- ferentiation following repeated damage of a tissue and subsequent regeneration can give rise to the emergence of tumors. 1 As TH Morgan proposed, regeneration could be regarded as “a by-product, an epi- phenimenon of the mechanisms underly- ing the development and maintenance of a particular structure […].” 9 However, most of the examples of cell reprogramming come from experimental manipulation and only rare developmental cases of cell-fate switching have been described. This may account for the fact that cell-fate switching requires extremely precise control during development in order to avoid drastic pat- terning defects and tissue malformation. A developmental epithelial to neuronal transdifferentiation case has recently been reported in Caenorhabditis elegans, the role of which remains elusive. 10 During early development, cell-fate switching is concomitant with lineage specification during segment boundary sharpening in Drosophila 11 and hindbrain segmentation and somitogenesis in vertebrates. 12-17 Very recently, we reported a unique case of highly stereotyped developmental cell reprogramming leading to compart- ment mixing which occurs during late Drosophila melanogaster embryogenesis. 18 Mixer Cell Formation as a New Developmental Model of Reprogramming A well-studied developmental model of epithelial sealing in Drosophila,