FGF5 is a crucial regulator of hair length in humans

Higgins, Claire A.; Petukhova, Lynn; Harel, Sivan; Ho, Yuan Y.; Drill, Esther; Shapiro, Lawrence; Wajid, Muhammad; Christiano, Angela M.

doi:10.1073/pnas.1402862111

Cited by 141 publications

(123 citation statements)

References 45 publications

(36 reference statements)

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“…FGF5 plays an important role in the regulation of anagen-to-catagen transition and the control of human hair length202122. DKK2 encodes for a member of the family of dickkopf WNT-signalling inhibitors, which are reported to be secreted by dermal papilla cells Fig.…”

Section: Resultsmentioning

confidence: 99%

Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness

et al. 2017

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Male-pattern baldness (MPB) is a common and highly heritable trait characterized by androgen-dependent, progressive hair loss from the scalp. Here, we carry out the largest GWAS meta-analysis of MPB to date, comprising 10,846 early-onset cases and 11,672 controls from eight independent cohorts. We identify 63 MPB-associated loci (P<5 × 10−8, METAL) of which 23 have not been reported previously. The 63 loci explain ∼39% of the phenotypic variance in MPB and highlight several plausible candidate genes (FGF5, IRF4, DKK2) and pathways (melatonin signalling, adipogenesis) that are likely to be implicated in the key-pathophysiological features of MPB and may represent promising targets for the development of novel therapeutic options. The data provide molecular evidence that rather than being an isolated trait, MPB shares a substantial biological basis with numerous other human phenotypes and may deserve evaluation as an early prognostic marker, for example, for prostate cancer, sudden cardiac arrest and neurodegenerative disorders.

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Section: Resultsmentioning

confidence: 99%

Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness

et al. 2017

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“…Similarly, mutations within the FGF5 gene are associated with hair length in cats (Drögemüller et al, 2007;Kehler et al, 2007). Using a combination of whole-exome sequencing and homozygosity mapping, Higgins et al (2014) identified distinct pathogenic mutations within the human FGF5 gene in several additional trichomegaly families. FGF5 was also identified to be a crucial regulator of hair growth in humans.…”

Section: Introductionmentioning

confidence: 99%

Cloning, molecular characterization, and expression pattern of FGF5 in Cashmere goat (Capra hircus)

Bao¹,

Yao²,

He³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Fibroblast growth factor 5 (FGF5) is a secreted signaling protein that belongs to the FGF family, and was found to be associated with hair growth in humans and other animals. The Inner Mongolia Cashmere goat (Capra hircus) is a goat breed that provides superior cashmere; this breed was formed by spontaneous mutation in China. Here, we report the cloning, molecular characterization, and expression pattern of the Cashmere goat FGF5. The cloned FGF5 cDNA was 813 base pairs (KM596772), including an open reading frame encoding a 270-amino-acid polypeptide. The nucleotide sequence shared 99% homology with Ovis aries FGF5 (NM_001246263.1). Bioinformatic analysis revealed that FGF5 contained a signal peptide, an FGF domain, and a heparin-binding growth factor/FGF family signature. There was 1 cAMP-and cGMP-dependent protein kinase phosphorylation site, 11 protein kinase C phosphorylation sites, 4 casein kinase II phosphorylation sites, 1 amidation site, 1 N-glycosylation site, and 1 tyrosine kinase phosphorylation site in FGF5. Real-time polymerase chain reaction showed that FGF5 mRNA levels were higher in testis than in the pancreas and liver. These data suggest that FGF5 may play a crucial role in Cashmere goat hair growth.

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“…This is evident by the striking phenotypic similarities between human congenital disorders caused by alterations in Fgf signaling and their corresponding mouse models. Conserved developmental requirements have been demonstrated in skeletal growth, palate closure, limb patterning, ear development, cranial suture ossification, neural development, and the hair cycle (Hebert et al 1994;Rousseau et al 1994;Shiang et al 1994;Wilkie et al 1995;Partanen et al 1998;Chen et al 1999;Li et al 1999;Wang et al 1999Wang et al , 2005Dode et al 2003;Tsai et al 2005;Gill and Tsai 2006;Mason 2007;Riley et al 2007;Falardeau et al 2008;Mansour et al 2009;Stanier and Pauws 2012;Simonis et al 2013;Higgins et al 2014;Ornitz and Marie 2015). These conserved developmental functions and accessible genetics make the mouse an excellent model for studying the mechanisms that Fgf signaling uses in vivo, which we discuss in this review.…”

mentioning

confidence: 99%

Genetic insights into the mechanisms of Fgf signaling

2016

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The fibroblast growth factor (Fgf) family of ligands and receptor tyrosine kinases is required throughout embryonic and postnatal development and also regulates multiple homeostatic functions in the adult. Aberrant Fgf signaling causes many congenital disorders and underlies multiple forms of cancer. Understanding the mechanisms that govern Fgf signaling is therefore important to appreciate many aspects of Fgf biology and disease. Here we review the mechanisms of Fgf signaling by focusing on genetic strategies that enable in vivo analysis. These studies support an important role for Erk1/2 as a mediator of Fgf signaling in many biological processes but have also provided strong evidence for additional signaling pathways in transmitting Fgf signaling in vivo.

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FGF5 is a crucial regulator of hair length in humans

Cited by 141 publications

References 45 publications

Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness

Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness

Cloning, molecular characterization, and expression pattern of FGF5 in Cashmere goat (Capra hircus)

Genetic insights into the mechanisms of Fgf signaling

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