Dataset Information

Crosstalk between androgen and Wnt/?-catenin leads to changes of wool density in FGF5-knockout sheep.

ABSTRACT: Fibroblast growth factor 5 (FGF5) is a famous dominant inhibitor of anagen phase of hair cycle. Mutations of FGF5 gene result in a longer wool in mice, donkeys, dogs, cats, and even in human eyelashes. Sheep is an important source of wool production. How to improve the production of wool quickly and effectively is an urgent problem to be solved. In this study, we generated five FGF5-knockout Dorper sheep by the CRISPR/Cas9 system. The expression level of FGF5 mRNA in knockout (KO) sheep decreased significantly, and all FGF5 proteins were dysfunctional. The KO sheep displayed a significant increase in fine-wool and active hair-follicle density. The crosstalk between androgen and Wnt/?-catenin signaling downstream of FGF5 gene plays a key role. We established downstream signaling cascades for the first time, including FGF5, FGFR1, androgen, AR, Wnt/?-catenin, Shh/Gli2, c-MYC, and KRTs. These findings further improved the function of FGF5 gene, and provided therapeutic ideas for androgen alopecia.

SUBMITTER: Zhang R

PROVIDER: S-EPMC7260202 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Crosstalk between androgen and Wnt/β-catenin leads to changes of wool density in FGF5-knockout sheep.

Zhang Rui R Li Yan Y Jia Kun K Xu Xueling X Li Yao Y Zhao Yue Y Zhang Xiaosheng X Zhang Jinlong J Liu Guoshi G Deng Shoulong S Lian Zhengxing Z

Cell death & disease 20200529 5

Fibroblast growth factor 5 (FGF5) is a famous dominant inhibitor of anagen phase of hair cycle. Mutations of FGF5 gene result in a longer wool in mice, donkeys, dogs, cats, and even in human eyelashes. Sheep is an important source of wool production. How to improve the production of wool quickly and effectively is an urgent problem to be solved. In this study, we generated five FGF5-knockout Dorper sheep by the CRISPR/Cas9 system. The expression level of FGF5 mRNA in knockout (KO) sheep decrease ...[more]

PMID: 32472005

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Project description:Fibroblast growth factor 5 (FGF5) gene, a member of fibroblast growth factor superfamily, plays significant roles in the regulation of the hair growth cycle during the development of mammalian hair follicles as well as the skeletal muscle development. In this study, DNA sequencing was used to scan the putative SNPs within the full-length of FGF5 gene, and SNPscan high-throughput technique was applied in the individual genotyping of 604 crossbred sheep. 10 SNPs were identified within FGF5 gene while five of them located in intron 1 could be genotyped, namely SNP1 (g. 105914953 G > A), SNP2 (g. 105922232 T > C), SNP3 (g. 105922244 A > G), SNP4 (g. 105922334 A > T) and SNP5 (g. 105922340 G > T). All these SNPs were in accord with the Hardy-Weinberg equilibrium (P > 0.05), and displayed the moderate polymorphism with PIC values ranging from 0.302 to 0.374. Thereafter, the correlation analysis between each SNP locus and economic traits including wool length, greasy wool weight and growth performance of sheep was systematically implemented. In our results, SNP1, SNP3, SNP4 and SNP5 were significantly associated with wool length, greasy wool weight and growth traits of SG sheep (P < 0.05); SNP1, SNP2, SNP3, and SNP4 were significantly correlated with wool length and growth traits of SSG sheep (P < 0.05). Meanwhile, our study revealed a strong linkage disequilibrium (LD) relationship among these SNPs (r2 > 0.33), except for SNP3 and SNP4 sites (r2 = 0.30). Combination genotype analysis showed that combination genotypes were significantly associated with mean fiber diameter of SG (P < 0.05), and body weight trait of SSG (P < 0.01). The above findings suggested that these SNP loci might affect economic traits synergistically and could be regarded as potential molecular markers for improving both wool production and growth performance of fine-wool sheep, which lay a molecular foundation for the breeding of fine dual-purpose sheep thereby accelerating the pace of sheep breeding.

Project description:To investigate single nucleotide polymorphism (SNP) loci associated with yearling wool traits of fine-wool sheep for optimizing marker-assisted selection and dissection of the genetic architecture of wool traits, we conducted a genome-wide association study (GWAS) based on the fixed and random model circulating probability unification (FarmCPU) for yearling staple length (YSL), yearling mean fiber diameter (YFD), yearling greasy fleece weight (YGFW), and yearling clean fleece rate (YCFR) by using the whole-genome re-sequenced data (totaling 577 sheep) from the following four fine-wool sheep breeds in China: Alpine Merino sheep (AMS), Chinese Merino sheep (CMS), Qinghai fine-wool sheep (QHS), and Aohan fine-wool sheep (AHS). A total of 16 SNPs were detected above the genome-wise significant threshold (P = 5.45E-09), and 79 SNPs were located above the suggestive significance threshold (P = 5.00E-07) from the GWAS results. For YFD and YGFW traits, 7 and 9 SNPs reached the genome-wise significance thresholds, whereas 10 and 12 SNPs reached the suggestive significance threshold, respectively. For YSL and YCFR traits, none of the SNPs reached the genome-wise significance thresholds, whereas 57 SNPs exceeded the suggestive significance threshold. We recorded 14 genes located at the region of ±50-kb near the genome-wise significant SNPs and 59 genes located at the region of ±50-kb near the suggestive significant SNPs. Meanwhile, we used the Average Information Restricted Maximum likelihood algorithm (AI-REML) in the "HIBLUP" package to estimate the heritability and variance components of the four desired yearling wool traits. The estimated heritability values (h2) of YSL, YFD, YGFW, and YCFR were 0.6208, 0.7460, 0.6758, and 0.5559, respectively. We noted that the genetic parameters in this study can be used for fine-wool sheep breeding. The newly detected significant SNPs and the newly identified candidate genes in this study would enhance our understanding of yearling wool formation, and significant SNPs can be applied to genome selection in fine-wool sheep breeding.

Dataset Information

Crosstalk between androgen and Wnt/?-catenin leads to changes of wool density in FGF5-knockout sheep.

Publications

Crosstalk between androgen and Wnt/β-catenin leads to changes of wool density in FGF5-knockout sheep.

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