A pair of transmembrane receptors essential for the retention and pigmentation of hair

Han, Rong Xun; Beppu, Hideyuki; Lee, Yunkyoung; Georgopoulos, Katia; Larue, Lionel; Li, En; Weiner, Lorin; Brissette, Janice L.

doi:10.1002/dvg.22039

Cited by 13 publications

(15 citation statements)

References 67 publications

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“…Our focused signaling interaction analysis identified additional signals of particular interest: Nrg2 signaling from DP may activate Erbb3 in Mc, which is involved in Mc maturation and melanoma development (Buac et al, 2009). Similarly, DP-secreted Inhba could bind Acvr2a in Mc to modulate hair pigmentation, as Acvr2a and Bmpr2 ablation in Mc induces graying (Han et al, 2012). Also, Edar is known to activate Shh signaling through the NF-kB pathway (Schmidt-Ullrich et al, 2006), and could be the missing link between Eda secretion from DP and Shh production from TAC.…”

Section: Discussionmentioning

confidence: 99%

Signaling Networks among Stem Cell Precursors, Transit-Amplifying Progenitors, and their Niche in Developing Hair Follicles

et al. 2016

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SUMMARY The hair follicle (HF) is a complex miniorgan that serves as an ideal model system to study stem cell (SC) interactions with the niche during growth and regeneration. Dermal papilla (DP) cells are required for SC activation during the adult hair cycle, but signal exchange between niche and SC precursors/transit amplifying progenitor cells (TACs) that regulates HF morphogenetic growth is less explored. Here we use six transgenic reporters to isolate 14 major skin and HF cell populations. With next-generation RNA sequencing we characterize their transcriptomes and define unique molecular signatures. SC precursors, TACs and the DP niche express a plethora of ligands and receptors. Signaling interaction network analysis reveals a birds-eye view of pathways implicated in epithelial-mesenchymal interactions. Using a systematic tissue-wide approach this work provides a comprehensive platform, linked to an interactive online database, to identify and further explore the SC/TAC/niche crosstalk regulating HF growth.

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Section: Discussionmentioning

confidence: 99%

Signaling Networks among Stem Cell Precursors, Transit-Amplifying Progenitors, and their Niche in Developing Hair Follicles

et al. 2016

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“…Reduced Bmpr2/Acvr2a function in melanocytes in mutant mice was recently shown to result in gray hair due to aberrant hair shaft and melanosomes' differentiation. [44] Stem cell factor (SCF) and its receptor (KIT) were shown to have an important role in signaling in the maintenance of human hair follicle melanogenesis during the anagen cycle and in physiological aging of the hair follicle pigmentary unit. [45] Both Notch 1 and Notch 2 signaling pathways are required for the maintenance of melanoblasts and melanocyte stem cells and are essential for proper hair pigmentation in mice.…”

Section: Pathogenesis Of Canities Pathogenesis Of Canitiesmentioning

confidence: 99%

Premature graying of hair

Pandhi¹,

Khanna²

2013

Indian J Dermatol Venereol Leprol

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Premature graying is an important cause of low self-esteem, often interfering with socio-cultural adjustment. The onset and progression of graying or canities correlate very closely with chronological aging, and occur in varying degrees in all individuals eventually, regardless of gender or race. Premature canities may occur alone as an autosomal dominant condition or in association with various autoimmune or premature aging syndromes. It needs to be differentiated from various genetic hypomelanotic hair disorders. Reduction in melanogenically active melanocytes in the hair bulb of gray anagen hair follicles with resultant pigment loss is central to the pathogenesis of graying. Defective melanosomal transfers to cortical keratinocytes and melanin incontinence due to melanocyte degeneration are also believed to contribute to this. The white color of canities is an optical effect; the reflection of incident light masks the intrinsic pale yellow color of hair keratin. Full range of color from normal to white can be seen both along individual hair and from hair to hair, and admixture of pigmented and white hair is believed to give the appearance of gray. Graying of hair is usually progressive and permanent, but there are occasional reports of spontaneous repigmentation of gray hair. Studies evaluating the association of canities with osteopenia and cardiovascular disease have revealed mixed results. Despite the extensive molecular research being carried out to understand the pathogenesis of canities, there is paucity of effective evidence-based treatment options. Reports of repigmentation of previously white hair following certain inflammatory processes and use of drugs have suggested the possibility of cytokine-induced recruitment of outer sheath melanocytes to the hair bulb and rekindled the hope for finding an effective drug for treatment of premature canities. In the end, camouflage techniques using hair colorants are outlined.

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“…38 Moreover, the redundancy of BMP type II receptors has also been described, in vivo, in retention and pigmentation of hair. 39 The contribution of BMP type II receptors to BMP signaling and the regulation of hepcidin gene expression differs from that of BMP type I receptors. Hepatocyte-specific deficiency of either ALK2 or ALK3 reduces basal hepcidin gene expression, as well as responsiveness to increased iron levels and BMP ligands.…”

Section: Discussionmentioning

confidence: 99%

BMP type II receptors have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism

Mayeur

Leyton

Kolodziej

et al. 2014

Blood

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Key Points• Presence of either ActR2a or BMPR2 in hepatocytes is sufficient to maintain hepatic hepcidin gene expression and iron metabolism.• Deficiency of both BMP type II receptors in hepatocytes induces iron overload.Expression of hepcidin, the hepatic hormone controlling iron homeostasis, is regulated by bone morphogenetic protein (BMP) signaling. We sought to identify which BMP type II receptor expressed in hepatocytes, ActR2a or BMPR2, is responsible for regulating hepcidin gene expression. We studied Bmpr2 heterozygous mice (Bmpr2 1/2 ), mice with hepatocyte-specific deficiency of BMPR2, mice with global deficiency of ActR2a, and mice in which hepatocytes lacked both BMPR2 and ActR2a. Hepatic hepcidin messenger RNA (mRNA) levels, serum hepcidin and iron levels, and tissue iron levels did not differ in wild-type mice, Bmpr2 1/2 mice, and mice in which either BMPR2 or ActR2a was deficient.Deficiency of both BMP type II receptors markedly reduced hepatic hepcidin gene expression and serum hepcidin levels leading to severe iron overload. Iron injection increased hepatic hepcidin mRNA levels in mice deficient in either BMPR2 or ActR2a, but not in mice deficient in both BMP type II receptors. In addition, in mouse and human primary hepatocytes, deficiency of both BMPR2 and ActR2a profoundly decreased basal and BMP6-induced hepcidin gene expression. These results suggest that BMP type II receptors, BMPR2 and ActR2a, have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism. (Blood. 2014;124(13):2116-2123

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A pair of transmembrane receptors essential for the retention and pigmentation of hair

Cited by 13 publications

References 67 publications

Signaling Networks among Stem Cell Precursors, Transit-Amplifying Progenitors, and their Niche in Developing Hair Follicles

Signaling Networks among Stem Cell Precursors, Transit-Amplifying Progenitors, and their Niche in Developing Hair Follicles

Premature graying of hair

BMP type II receptors have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism

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