Expression Of FOXC2 Transcription Factor On Human Embryo

Human forkhead box c2 (FOXC2),a member of the winged helixtranscription factors super family with DNA-binding domains, isevolutionarily highly conserved and located on 16q22-16q24. It ischaracterized by an independent DNA-binding domain. Many studies haveshown that FOXC2 mutation is related with many human genetic diseases. Ithas been known that FOXC2 transcription factor is closely associated withLymphoedema-Distichiasis syndrome (LD). Severe cases of this syndromealso have developmental anomalies of heart and axial skeleton, such as Fallot'stetrad, cleft palate. Some other studies have found that SNPs of this gene isrelated to obesity, lipid metabolism and insulin resistance. It has confirmedthat there is significant effect of Foxc2 transcription factor on genesis anddevelopment of mice embryo. Human FOXC2 proteins has a conservedDNA-binding domain of 100 amino acids being 94% homology with mouseFoxc2, so this gene should also play an essential regulatory role in humanembryo development. The mutations of FOXC2 gene maybe have certainassociation with congenital cardiovascular defects and developmental defect ofaxial skeleton.The current study analyzed the effect of FOXC2 gene on genesis anddevelopment of human embryo heart and axial skeleton usingimmunohistochemistry and in situ hybridization, which established thetheoretical foundation to further understand the association between this geneand congenital developmental defect. The results showed that FOXC2 of wasexpressed extensively in early pregnancy embryo;FOXC2 was over expressedin mesenchymal cell nucleus surrounding the dorsal chord near head anddorsal aorta. With the development and differentiation of embryo, theexpression of FOXC2 became local. The strong brown-yellow positive stain ofFOXC2 expression could be observed in the endothelial cell nucleus of dorsalaorta and its connected arcuate artery of the embryo. Embryo at gestationalage about 60 days, FOXC2 began to express in great vessels of heart,full-thickness of aorta, ventricular endocardium and outer sphere of ventricularwall. Later on, the expression of FOXC2 appeared in border cells of branchvessels of aorta, coronary artery, wall of great vessels and mesenchymal cellsaround vessels. After 12 weeks of gestational age, the expression of FOXC2was localized in middle or small vessel of embryo heart, and the expression inendothelial cells of great vessels declined obviously. As for skeletondevelopment, FOXC2 was significantly expressed in mesoderm at earlypregnancy which later developed into vertebral column and costal bone.Expression of FOXC2 is also strong at the site of segment cells that graduallyformed. Later pyramid and costal cartilage formed and FOXC2 could be foundin cartilage cell nucleus. After 80 days of gestational age, FOXC2 continued toexpress in pyramid cartilage and costal cartilage. Besides, FOXC2 alsoexpressed in the cartilage of embryonic bud of limbs. At the gestational age of3 months, pyramid gradually calcified, and FOXC2 expression only localizedin ossificationis of pyramid.The results of this studies suggested that the effect of FOXC2 onreforming of aorta, development and forming of vertebral column and costa aswell as moulding of bones of limbs could not be substituted.