Principles and mechanisms of regeneration in the mouse model for wound-induced hair follicle neogenesis.
Wound induced hair follicle neogenesis (WIHN) describes a regenerative phenomenon in adult mammalian skin, wherein fully functional hair follicles regeneratede novoin the center of large excisional wounds. Originally described in rats, rabbits, sheep, and humans in 1940-60, the WIHN phenomenon was reinvestigated in mice only recently. The process ofde novohair regeneration largely duplicates the morphological and signaling features of normal embryonic hair development. Similar to hair development, WIHN critically depends on the activation of canonical WNT signaling. However, unlike hair development, WNT activation in WIHN is dependent on Fgf9 signaling generated by the immune system's gamma delta (γδ) T cells. The cellular bases of WIHN remain to be fully characterized, however, the available evidence leaves open the possibility for a blastema-like mechanism, wherein epidermal and/or dermal wound cells undergo epigenetic reprogramming toward a more plastic, embryonic-like state.De novohair follicles do not regenerate from preexisting hair-fated bulge stem cells. This suggests that hair neogenesis is not driven by preexisting lineage-restricted progenitors, as is the case for amputation-induced mouse digit tip regeneration, but rather may require a blastema-like mechanism. The WIHN model is characterized by several intriguing features, which await further explanation. These include: (i) minimum wound size requirement for activating neogenesis, (ii) restriction of hair neogenesis to the wound's center, (iii) imperfect patterning outcomes, both in terms of neogenic hair positioning within the wound and in terms of their orientation. Future inquires into the WIHN process, made possible by a wide array of the available skin-specific genetic tools, will undoubtedly expand our understanding of the regeneration mechanisms in adult mammals.
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA ; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA ; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
Xiaojie
X
Wang
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA ; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA ; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
Tsai-Ching
TC
Hsi
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA ; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA ; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
Christian Fernando
CF
Guerrero-Juarez
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA ; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA ; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
Kim
K
Pham
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA ; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA ; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
Kevin
K
Cho
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.
Catherine D
CD
McCusker
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA ; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA ; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA ; Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Edwin S
ES
Monuki
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA ; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
Ken W Y
KW
Cho
UMR 967, Cellules Souches et Radiations, CEA - INSERM - Universités Paris 7 et Paris 11, CEA/DSV/IRCM/SCSR/LRTS, 92265 Fontenay-aux-Roses Cedex, France.
Denise L
DL
Gay
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA ; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA ; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
Maksim V
MV
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