| Background: Transforming growth factors (TGF) are known to play important roles in signal transduction and induction during the development of embryo, but their spatiotemporal expression patterns and function during the development of embryonic mouse heart are still controversial. In order to inquire further into the distribution of different TGFps during development of mouse embryo heart and their relationship with differentiation of myocardium, formation of valves and septation of embryonic heart, systematic studies were made on expression patterns of different TGFp isoforms.Methods: Serial sections of mouse embryos from embryonic day 9(ED9) to embryonic day 14(ED14) were stained with polyclonal antibodies against TGFβ1, TGFβ2 and TGFP3 and monoclonal antibodies against a-SMA, a-SCA.Results: Expression of TGFβ1 in ED9 mouse heart is restricted to the part of the outflow tract proximal to ventricle with particulate expression pattern and lower staining intensity, whereas expression of a-SMA and a-SCA in the outflow tract has reached to the branchial arteries at this time.At ED10, expression of TGFβ1 reaches to the bifurcation of the branchial arteries in the outflow tract with obvious increase in staining intensity, one day later than that of a-SMA and a-SCA. As development of the embryonic heart progresses, expression intensity of TGFβ1 in Myocardium continuously increases to reach its highest level at ED12, especially that part of the myocardium of outflow tract surrounding endocardial ridges shows stronger TGFβ1 staining. Form ED13 to ED14, expression of TGFP1 in myocardium of atrium and ventricle decreases greatly, except that part of outflow tract myocardium surrounding endocardial ridges.No TGFβ2 positive staining can be detected in ED9 heart, though the vessel wall of placental decidua shows stronger staining. At ED10, TGFβ2 expression can be found in developing heart, expression in myocardium of outflow tract is slightly stronger than that in atrium and ventricle, but mesenchymal cells in outflow tract ridges show lower staining intensity. Form ED11 to ED13, staining intensity of TGFβ2 in the myocardium and mesenchymal cells of heart decreases greatly, at ED13, the TGFβ2 positive cells can be detected only in endothelial cells of outflow tract and endothelial cells of semilunar valves.At ED9, expression of TGFP3 is weaker and no difference in staining intensity can be recognized in different parts of the heart. Similar to TGFβ1, expression of TGFP3 reaches its highest level at ED12. Between ED13 and ED14, expression intensity of TGFβ3 decreases, but stronger TGFβ3 expression in compact myocardium and trabecular myocardium of right ventricle, trabecular myocardium of left ventricle and myocardium of atrium persists to ED14. With increasing expression of TGFP2 and TGFβ3 inmyocardiums, both HE and immunohistochemical staining show that from ED10 to ED14, endothelial cells of cardiac ridge of outflow tract and semilunar valves become cuboidal, and show stronger TGFβ2 and TGFβ3 staining.Conclusion: Expression of transforming growth factor-βs in the mouse heart has specific spatiotemporal expression pattern. Expression of TGFβ3 is earlier, but expression of TGFβ1 and TGFβ2 in embryonic heart is obviously later than expression of a-SMA and a-SCA, suggesting that TGFβ1 and TGFβ2 do not influence the committed differentiation of embryonic myocardium. The fact that expression of transforming growth factors is confined to the period of ED9 to ED14 during which proliferation and differentiation of embryonic heart are active indicates that transforming growth factor isoforms may regulate proliferation and differentiation of embryonic myocardium. Strong expression of TGFpl in the myocardium surrounding endocardial ridges may suggest induction role to the formation of outflow cushion tissue. The expression of TGFβ2 and TGFβ3 can be found not only in developing myocardium but also in mesenchymal cells and endocardial cells, these results suggest that both TGFβ2... |
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