Hair follicle specific ACVR1/ALK2 critically affects skin morphogenesis and attenuates wound healing

Michael Sorkin; Shailesh Agarwal; Kavitha Ranganathan; Shawn Loder; David Cholok; David Fireman; John Li; Shuli Li; Bin Zhao; Yuji Mishina; Paul Cederna; Benjamin Levi

doi:10.1111/wrr.12549

Hair follicle specific ACVR1/ALK2 critically affects skin morphogenesis and attenuates wound healing

Michael Sorkin, Shailesh Agarwal, Kavitha Ranganathan, Shawn Loder, David Cholok, David Fireman, John Li, Shuli Li, Bin Zhao, Yuji Mishina, Paul Cederna, Benjamin Levi^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	521-525
Number of pages	5
Journal	Wound Repair and Regeneration
Volume	25
Issue number	3
DOIs	https://doi.org/10.1111/wrr.12549
State	Published - 1 May 2017
Externally published	Yes

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title = "Hair follicle specific ACVR1/ALK2 critically affects skin morphogenesis and attenuates wound healing",

abstract = "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.",

author = "Michael Sorkin and Shailesh Agarwal and Kavitha Ranganathan and Shawn Loder and David Cholok and David Fireman and John Li and Shuli Li and Bin Zhao and Yuji Mishina and Paul Cederna and Benjamin Levi",

note = "Publisher Copyright: {\textcopyright} 2017 by the Wound Healing Society",

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doi = "10.1111/wrr.12549",

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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

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.

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JO - Wound Repair and Regeneration

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IS - 3

ER -

Hair follicle specific ACVR1/ALK2 critically affects skin morphogenesis and attenuates wound healing

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