Citazione:Messaggio inserito da Blackhead
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http://www.repubblica.it/2007/05/sezioni/scienza_e_tecnologia/calvi-pillola/calvi-pillola/calvi-pillola.html[X]
Li' non dice quasi niente...guardate qui invece:
http://www.venetonanotech.it/files/index.cfm?id_rst=31&id_elm=1602
e anche il nuovo articolo della repubblica che non dice le solite
cavolate generiche, ma è stato corretto ed integrato:
http://www.repubblica.it/2007/05/sezioni/scienza_e_tecnologia/calvizie/calvizie/calvizie.html
invece qui c'e' l'articolo originale di nature:
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Nature 447, 316-320 (17 May 2007) | doi:10.1038/nature05766; Received 30 August 2006; Accepted 20 March 2007
Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding
Mayumi Ito1, Zaixin Yang1, Thomas Andl1, Chunhua Cui1, Noori Kim1, Sarah E. Millar1 & George Cotsarelis1
Department of Dermatology, Kligman Laboratories, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
Correspondence to: George Cotsarelis1 Correspondence and requests for materials should be addressed to G.C. (Email: cotsarel@mail.med.upenn.edu).
Top of pageAbstractThe mammalian hair follicle is a complex 'mini-organ' thought to form only during development1; loss of an adult follicle is considered permanent. However, the possibility that hair follicles develop de novo following wounding was raised in studies on rabbits2, 3, mice4 and even humans fifty years ago5. Subsequently, these observations were generally discounted because definitive evidence for follicular neogenesis was not presented6. Here we show that, after wounding, hair follicles form de novo in genetically normal adult mice. The regenerated hair follicles establish a stem cell population, express known molecular markers of follicle differentiation, produce a hair shaft and progress through all stages of the hair follicle cycle. Lineage analysis demonstrated that the nascent follicles arise from epithelial cells outside of the hair follicle stem cell niche, suggesting that epidermal cells in the wound assume a hair follicle stem cell phenotype. Inhibition of Wnt signalling after re-epithelialization completely abrogates this wounding-induced follic**ogenesis, whereas overexpression of Wnt ligand in the epidermis increases the number of regenerated hair follicles. These remarkable regenerative capabilities of the adult support the notion that wounding induces an embryonic phenotype in skin, and that this provides a window for manipulation of hair follicle neogenesis by Wnt proteins. These findings suggest treatments for wounds, hair loss and other degenerative skin disorders.
During our studies on wound healing in mice, we noticed structures within the centre of large healing wounds that resembled early developing hair follicles. To characterize these structures, we performed timed experiments in which a 1 cm2 square of full-thickness back skin was excised from 3-week-old mice, at least 2 weeks after the last hair follicles had formed. By 10–11 days after wounding, contracture and re-epithelialization resulted in wound closure and an approximately 0.25 cm2 area composed of an epidermis and a dermis with no evidence of hair follicles (Fig. 1a). At 14–19 days after wounding, small epidermal downgrowths that resembled developing embryonic hair follicles were present (Fig. 1d–h). Older (7–8-week-old to 10-month-old) mice also showed hair follicle neogenesis after wounding, but larger wounds (2.25 cm2) were required to trigger follicle formation (Supplementary Table 1). The final rather than initial size of the wound seemed to correlate with hair follicle neogenesis because the larger wound in older mice also yielded a 0.25 cm2 area immediately after re-epithelialization. (Further characterization of hair follicle neogenesis with respect to density, type and orientation of the hair follicles is presented in Supplementary Table 2, Supplementary Figs 1–3 and Supplementary Notes 1, 2.)
Figure 1: Hair follicle regeneration recapitulates embryonic development.
a–c, Hair appears in the re-epithelialized wound after several weeks. Scale bar, 1 mm. d–h, Histology of skin after wounding shows regenerating hair follicles mimicking stages of normal embryonic hair follicle development (examples shown in insets d–f). Sebaceous gland (arrowhead, h) also regenerates from the new follicle (h, inset, sebaceous gland stained with oil red O). hs, hair shaft. i–o, Nascent hair follicles proliferate and express genes and proteins (as indicated) that are associated with hair follicle differentiation, as detected by immunostaining (i), BrdU detection (l), in situ hybridization (j, n, o), alkaline phosphatase activity (k) and RT–PCR (m). Arrows point to signal. Scale bars, d–l, n, o, 50 m. Time after wounding is in days (d). M, DNA size marker.
High resolution image and legend (612K)
Hair follicles consist of at least ten different epithelial and mesenchymal cell types geared towards the production of hair7. In the embryo, hair follicle development begins with the formation of a small cluster of epidermal cells (epithelial placode) that can be detected by expression of cytokeratin 17 (KRT17), an intermediate filament protein8. Placodes overlie a dermal condensate, which is identified by alkaline phosphatase activity9. Through a series of mesenchymal–epithelial interactions initiated by activation of Wnt and requiring downstream Shh signalling, placode cells proliferate, move downward and engulf the dermal condensate, eventually forming a mature follicle that cyclically produces hair throughout life10.
We discovered that hair follicle neogenesis following wounding paralleled embryonic follicle development at the molecular level. The regenerated hair follicles expressed KRT17, Lef1, alkaline phosphatase, Wnt10b and Shh (Fig. 1i–o), which is analogous to embryonic follicles10. The truly nascent nature of these follicles was demonstrated by absence of expression (by PCR with reverse transcription; RT–PCR) of hair follicle differentiation markers KRT17 (ref. 8) and Lef1 (refs 10, 11) in the epidermis for several days after wound closure (Fig. lm), and their subsequent appearance coinciding with the development of hair germs and pegs (Fig. li, j, m). The newly formed hair follicles also proliferated normally (Fig. 1l) and generated hair as well as sebaceous glands (Fig. 1c, h).
We asked next whether the de novo follicles arise from hair follicle stem cells in skin bordering the wound. Hair follicle stem cells have been localized to the bulge area12, 13, and bulge cells in follicles surrounding a 4 mm wound send progeny towards the centre of the wound during re-epithelialization14, 15. However, the majority of bulge cell progeny contribute transiently to the new epidermis and do not persist beyond three weeks14. To investigate whether the nascent follicles that developed following larger wounds originated from hair follicle stem cells, we performed genetic lineage analysis using inducible Tg(Krt1-15-cre/PGR)22Cot;R26R transgenic mice (Fig. 2, Supplementary Fig. 4 and Supplementary Table 3)13, 14. These mice express CrePR1, a fusion protein consisting of Cre-recombinase and a truncated progesterone receptor that binds the progesterone antagonist RU486 under the control of the Krt1-15 promoter, which is active predominantly in bulge cells of adult mouse skin13, 16. Treatment of adult Tg(Krt1-15-cre/PGR)22Cot;R26R mice with RU486 resulted in permanent expression of lacZ in bulge cells and in all progeny of labelled bulge cells13, 14. We discovered that although bulge cell progeny migrated to the centre of the larger wounds, they di