TY - JOUR
T1 - Hair follicle specific ACVR1/ALK2 critically affects skin morphogenesis and attenuates wound healing
AU - Sorkin, Michael
AU - Agarwal, Shailesh
AU - Ranganathan, Kavitha
AU - Loder, Shawn
AU - Cholok, David
AU - Fireman, David
AU - Li, John
AU - Li, Shuli
AU - Zhao, Bin
AU - Mishina, Yuji
AU - Cederna, Paul
AU - Levi, Benjamin
N1 - Funding Information:
Source of Funding: B.L. was funded by 1K08GM109105-01, Plastic Surgery Foundation National Endowment Award, American Association of Plastic Surgery Award, American Association for the Surgery of Trauma, and the Association of Academic Surgery. S.L. was funded by a Howard Hughes Medical Institute research fellowship. K.R. was funded by NIH 1F32AR068902-01 and Frederick A. Coller Society. S.A. was funded by the NIH LRP, Coller Society, and Plastic Surgery Foundation. K.R. was supported by the Coller Society Research Fellowship, NIH, F32 1-F32-AR-068902-01, and American Society of Maxillofacial Surgery. S.A. was supported by the Coller Society Research Fellowship, NIH Loan Repayment Program, NIH, F32AR06649901A1 and Plastic Surgery Foundation. S.L. was supported by the Howard Hughes Medical Institute (HHMI) Medical Fellows Program.
Publisher Copyright:
© 2017 by the Wound Healing Society
PY - 2017/5/1
Y1 - 2017/5/1
N2 - The bone morphogenic protein signaling (BMP) is intricately involved in the quiescence and regulation of stem cells through activation of BMP receptors. Hair follicle stem cells play a critical role in cutaneous homeostasis and regeneration. Here, we utilize a novel mouse model with targeted overexpression of the BMP receptor ALK2/ACVR1 in hair follicle stem cells, to characterize its role in skin development and postnatal wound healing. Initial histologic evaluation demonstrated significant dysregulation in hair follicle morphogenesis in mutant mice. These demonstrated increased numbers of individual hair follicles with altered morphology and localization. Mutant follicles were found to exhibit elevated proliferative activity as well as increased prevalence of CD34 and ITGA6 positive follicle stem cells. Interestingly, constitutive overexpression of ALK2 resulted in attenuation of cutaneous wound healing. These findings demonstrate that hair follicle specific ALK2 is intricately involved in maintenance of the stem cell niche and wound healing.
AB - The bone morphogenic protein signaling (BMP) is intricately involved in the quiescence and regulation of stem cells through activation of BMP receptors. Hair follicle stem cells play a critical role in cutaneous homeostasis and regeneration. Here, we utilize a novel mouse model with targeted overexpression of the BMP receptor ALK2/ACVR1 in hair follicle stem cells, to characterize its role in skin development and postnatal wound healing. Initial histologic evaluation demonstrated significant dysregulation in hair follicle morphogenesis in mutant mice. These demonstrated increased numbers of individual hair follicles with altered morphology and localization. Mutant follicles were found to exhibit elevated proliferative activity as well as increased prevalence of CD34 and ITGA6 positive follicle stem cells. Interestingly, constitutive overexpression of ALK2 resulted in attenuation of cutaneous wound healing. These findings demonstrate that hair follicle specific ALK2 is intricately involved in maintenance of the stem cell niche and wound healing.
UR - http://www.scopus.com/inward/record.url?scp=85021269735&partnerID=8YFLogxK
U2 - 10.1111/wrr.12549
DO - 10.1111/wrr.12549
M3 - Article
C2 - 28513105
AN - SCOPUS:85021269735
SN - 1067-1927
VL - 25
SP - 521
EP - 525
JO - Wound Repair and Regeneration
JF - Wound Repair and Regeneration
IS - 3
ER -