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 gr...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.展开更多
Objective:Congenital heart disease(CHD)is caused by abnormal cardiac development,which is the most common congenital malformation at home and abroad.NKX2-5,GATA4 and ZIC3 have been shown to be associated with CHD.This...Objective:Congenital heart disease(CHD)is caused by abnormal cardiac development,which is the most common congenital malformation at home and abroad.NKX2-5,GATA4 and ZIC3 have been shown to be associated with CHD.This experiment explored the relationship between NKX2-5,GATA4 and ZIC3 gene mutations and sporadic CHD in Hainan Province.Methods:To collect 210 sporadic CHD patients in Hainan,the DNA of patients was extracted from blood,and the target gene fragments were amplified.Using high-resolution melting(HRM)and DNA sequencing technology,and we analyzed the sequences of NKX2-5,GATA4 and ZIC3 genes.Results:NKX2-5,GATA4 and ZIC3 genes were sequenced in 210 CHD patients,and seven gene mutations were found,including NKX2-5 heterozygous missense mutation(c.178G>T)and three heterozygous mutations in GATA4(c.677C>T,c.928A>G,c.1123G>A),three heterozygous mutations in ZIC3(c.19G>C,c.1255C>G,c.1348C>T),in which NKX2-5(c.178G>T),GATA4(c.1123G>A),and ZIC3(c.1255C>G,c.1348C>T)are new mutation sites.These gene mutations were predicted to be pathogenic mutations by bioinformatics software.Conclusion:Conclusion:Seven gene mutations were found in 210 patients,and it was the first report that the gene mutations of NKX2-5,GATA4 and ZIC3 in Hainan Province associated with the pathogenesis of CHD.展开更多
基金supported by the Department of Science&Technology of Liaoning Province(2024-MS-099,2024-BS-093)。
文摘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.
基金Natural Science Foundation of Hainan Province(No.821RC562)Re-research Project of Hainan Province(No.ZDYF2022SHF2081)+1 种基金National Natural Science Foundation of China(No.81660224)Graduate Innovation Project of Hainan Province(No.Qhys2021-353)。
文摘Objective:Congenital heart disease(CHD)is caused by abnormal cardiac development,which is the most common congenital malformation at home and abroad.NKX2-5,GATA4 and ZIC3 have been shown to be associated with CHD.This experiment explored the relationship between NKX2-5,GATA4 and ZIC3 gene mutations and sporadic CHD in Hainan Province.Methods:To collect 210 sporadic CHD patients in Hainan,the DNA of patients was extracted from blood,and the target gene fragments were amplified.Using high-resolution melting(HRM)and DNA sequencing technology,and we analyzed the sequences of NKX2-5,GATA4 and ZIC3 genes.Results:NKX2-5,GATA4 and ZIC3 genes were sequenced in 210 CHD patients,and seven gene mutations were found,including NKX2-5 heterozygous missense mutation(c.178G>T)and three heterozygous mutations in GATA4(c.677C>T,c.928A>G,c.1123G>A),three heterozygous mutations in ZIC3(c.19G>C,c.1255C>G,c.1348C>T),in which NKX2-5(c.178G>T),GATA4(c.1123G>A),and ZIC3(c.1255C>G,c.1348C>T)are new mutation sites.These gene mutations were predicted to be pathogenic mutations by bioinformatics software.Conclusion:Conclusion:Seven gene mutations were found in 210 patients,and it was the first report that the gene mutations of NKX2-5,GATA4 and ZIC3 in Hainan Province associated with the pathogenesis of CHD.
