Specific deletion of Axin1 leads to activation of beta-catenin/BMP signaling resulting in fibular hemimelia phenotype in mice

Xie, Rong1; Yi, Dan2,3; Zeng, Daofu2; Jie, Qiang4; Kang, Qinglin5; Zhang, Zeng5; Zhang, Zhenlin6; Xiao, Guozhi7; Chen, Lin8; Tong, Liping2; Chen, Di2,3

2022-12-21

10.7554/eLife.80013

eLife   Impact Factor & Quartile

2050-084X

Axin1 is a key regulator of canonical Wnt signaling pathway. Roles of Axin1 in skeletal development and in disease occurrence have not been fully defined. Here, we report that Axin1 is essential for lower limb development. Specific deletion of Axin1 in limb mesenchymal cells leads to fibular hemimelia (FH)-like phenotype, associated with tarsal coalition. Further studies demonstrate that FH disease is associated with additional defects in Axin1 knockout (KO) mice, including decreased osteoclast formation and defects in angiogenesis. We then provide in vivo evidence showing that Axin1 controls limb development through both canonical beta-catenin and BMP signaling pathways. We demonstrate that inhibition of beta-catenin or BMP signaling could significantly reverse the FH phenotype in mice. Together, our findings reveal that integration of beta-catenin and BMP signaling by Axin1 is required for lower limb development. Defect in Axin1 signaling could lead to the development of FH disease.

mice rat human Mouse

SCI

English

NI Journal Papers

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National Natural Science Foundation of China["82030067","82161160342","82172397","81974320"] ; National Key Research and Development Program of China[2021YFB3800800] ; Guangdong Basic and Applied Basic Research Foundation[2021A1515111075]

Life Sciences & Biomedicine - Other Topics

Biology

WOS:000933081700001

eLIFE SCIENCES PUBL LTD

Web of Science

1.Rush Univ, Dept Orthoped Surg, Med Ctr, Chicago, IL USA
2.Chinese Acad Sci, Shenzhen Inst Adv Technol, Res Ctr Comp Aided Drug Discovery, Shenzhen, Peoples R China
3.Chinese Acad Sci, Shenzhen Inst Adv Technol, Fac Pharmaceut Sci, Shenzhen, Peoples R China
4.Xi An Jiao Tong Univ, Honghui Hosp, Coll Med, Dept Orthoped Surg, Xian, Peoples R China
5.Shanghai Jiao Tong Univ, Dept Orthoped Surg, Affiliated Peoples Hosp 6, Shanghai, Peoples R China
6.Shanghai Jiao Tong Univ, Dept Osteoporosis & Bone Dis, Affiliated Peoples Hosp 6, Shanghai, Peoples R China
7.Southern Univ Sci & Technol, Sch Med, Shenzhen, Peoples R China
8.Army Med Univ, Daping Hosp, Dept Wound Repair & Rehabil, State Key Lab Trauma & Combined Injury, Chongqing, Peoples R China

Xie, Rong,Yi, Dan,Zeng, Daofu,et al. Specific deletion of Axin1 leads to activation of beta-catenin/BMP signaling resulting in fibular hemimelia phenotype in mice[J]. eLife,2022,11.

Xie, Rong.,Yi, Dan.,Zeng, Daofu.,Jie, Qiang.,Kang, Qinglin.,...&Chen, Di.(2022).Specific deletion of Axin1 leads to activation of beta-catenin/BMP signaling resulting in fibular hemimelia phenotype in mice.eLife,11.

Xie, Rong,et al."Specific deletion of Axin1 leads to activation of beta-catenin/BMP signaling resulting in fibular hemimelia phenotype in mice".eLife 11(2022).