ORIGINAL ARTICLE Ingrid Fliniaux . Jean P. Viallet . Danielle Dhouailly . Colin A. B. Jahoda Transformation of amnion epithelium into skin and hair follicles Received September 20, 2004; accepted in revised form October 7, 2004 Abstract There is increasing interest into the extent to which epithelial differentiation can be altered by me- senchymal influence, and the molecular basis for these changes. In this study, we investigated whether amnion epithelium could be transformed into skin and hair fol- licles by associating E12.5 to E14.5 mouse amnion from the ROSA 26 strain, with mouse embryonic hair-form- ing dermis from a wild-type strain. These associations were able to produce fully formed hair follicles with associated sebaceous glands, and skin epidermis. Using b-galactosidase staining we were able to demonstrate that the follicular epithelium and skin epidermis, but not the associated dermal cells, originated from the amnion. As Noggin and Sonic hedgehog (Shh) were recently shown to be required for early chick ventral skin formation, and able to trigger skin and feather formation from chick amnion, we associated cells en- gineered to produce those two factors with mouse am- nion. In a few cases, we obtained hair buds connected to a pluristratified epithelium; however, the transforma- tion of the amnion was impeded by uncontrolled fib- roblastic proliferation. In contrast to an earlier report, none of our control amnion specimens autonomously transformed into skin and hair follicles, indicating that specific influences are necessary to elicit follicle forma- tion from the mouse amnion. The ability to turn am- nion into skin and its appendages has practical potential for the tissue engineering of replacement skin, and re- lated biotechnological approaches. Key words amnion  mouse  dermis  epidermis  hair follicle  somatopleure  Noggin  Shh  skin replacement  plasticity  epithelial stem cells Introduction Within epithelial cell biology it has become increasingly evident, and is now widely accepted, that cells can un- dergo transition from one epithelial cell type to another. Previously, a more popular belief was that epithelial stem cell populations from specific regions such as the cornea and interfollicular epidermis were committed to give rise to only one particular derivative (Miller et al., 1993). Work on follicular epithelial stem cells has partly helped to dispel this view. It is well established that in the clinical context of wound repair and skin grafting, follicle epithelium is an important source of replace- ment epidermis. More recently, experimental evidence from labelling and transplantation studies has shown that follicular stem cells may also act in the normal physio- logical replacement of epidermis (Taylor et al., 2000; Oshima et al., 2001). Indeed, recent studies have shown that genetically labelled follicular stem cells can reconsti- tute all the differentiated compartments of skin and hair follicles (Morris et al., 2004) and that even committed cells from the follicle stem cell compartment, the bulge, can reconstitute hair and skin (Blanpain et al., 2004). From our perspective and experimental background, reprogramming activities such as those described above are not surprising, nor should they be considered in isolation. In general, the fate of epithelial cells is ulti- mately dictated by dermal influences. Indeed, a large body of tissue recombination experiments extending 1 Present address: Institute of Biotechnology, Viikki Biocenter, University of Helsinki, Finland. Ingrid Fliniaux 1  Jean P. Viallet  Danielle Dhouailly Equipe Biologie de la Diffe´renciation Epithe´liale UMR CNRS 5538 LEDAC, Institut Albert Bonniot Universite´ Joseph Fourier Grenoble, France Colin A. B. Jahoda ( . *) School of Biological and Biomedical Sciences University of Durham Durham, UK Tel: 44 191 334 1338 Fax: 44 191 334 1201 E-mail: colin.jahoda@durham.ac.uk U.S. Copyright Clearance Center Code Statement: 0301–4681/2004/7209–10–558 $ 15.00/0 Differentiation (2004) 72:558–565 r International Society of Differentiation 2004