Zic3 represses anterior digit development in tetrapodsOACSCDCSTPCD
Pentadactyl limbs represent a conserved morphological feature among tetrapods,with anterior digits considered more important than posterior digits for refined movement.While posterior digit formation is governed by graded expression of the Shh and 5’Hox genes,the regulatory mechanisms underlying anterior digit development,especially digit I(DI),remain poorly defined.This study identified an anterior expression pattern of Zic3 in the limb buds of representative tetrapods,including humans,which exerted an inhibitory effect on skeletal development.Zic3 was highly expressed in the anterior region of limb buds at early developmental stages,with species-specific divergence emerging during later development.Overexpression of Zic3 significantly delayed chondrogenesis and ossification,leading to bone shortening but not loss.Furthermore,RNA sequencing demonstrated that Zic3 down-regulated key genes associated with skeletal development,including Cytl1,Sox9,Ihh,Ptch1,Runx2,and Wnt16.These findings demonstrate that Zic3 acts as a conserved inhibitor of anterior skeletal maturation and contributes to the molecular asymmetry of tetrapod limb development.
Shan-Shan Li;Shi-Bin Bai;Xiao-Fei Sun;Cheng-Hua Yu;Yi-Ning Tang;Zi-Qiu Jia;Xiao-Ping Li;Song-Yang Shang;David MIrwin;Jun Li;Zhe Wang
College of Animal Science and Veterinary Medicine,Shenyang Agricultural University,Shenyang,Liaoning 110866,ChinaCollege of Animal Science and Veterinary Medicine,Shenyang Agricultural University,Shenyang,Liaoning 110866,ChinaDepartment of Obstetrics and Gynecology,Shengjing Hospital of China Medical University,Shenyang,Liaoning 110004,ChinaDepartment of Obstetrics and Gynecology,Shengjing Hospital of China Medical University,Shenyang,Liaoning 110004,ChinaCollege of Animal Science and Veterinary Medicine,Shenyang Agricultural University,Shenyang,Liaoning 110866,ChinaCollege of Animal Science and Veterinary Medicine,Shenyang Agricultural University,Shenyang,Liaoning 110866,ChinaCollege of Animal Science and Veterinary Medicine,Shenyang Agricultural University,Shenyang,Liaoning 110866,ChinaCollege of Animal Science and Veterinary Medicine,Shenyang Agricultural University,Shenyang,Liaoning 110866,ChinaDepartment of Laboratory Medicine and Pathobiology,University of Toronto,Toronto,Ontario M5S 1A8,CanadaDepartment of Obstetrics and Gynecology,Shengjing Hospital of China Medical University,Shenyang,Liaoning 110004,ChinaCollege of Animal Science and Veterinary Medicine,Shenyang Agricultural University,Shenyang,Liaoning 110866,China
生物科学
TetrapodZic3Limb developmentAnterior digitsTranscriptome
《Zoological Research》 2025 (3)
P.684-694,11
supported by the Department of Science&Technology of Liaoning Province(2024-MS-099,2024-BS-093)。
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