AAS ›› 2015, Vol. 46 ›› Issue (5): 649-654.doi: 10.16098/j.issn.0529-1356.2015.05.013

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Contributions of bone morphogenetic protein -2 to a cardiac outflow tract in the development of the mouse embryo

QU Xu-kuan HONG Xiao-yang JING Ya YANG Yan-ping XU Zhi-hui CUI Hui-lin QIAO Cong-jin LI Hai-rong*   

  1. Department of Histology and Embryology of Shanxi Medical University, Taiyuan 030001, China
  • Received:2015-02-09 Revised:2015-03-19 Online:2015-10-06 Published:2015-10-06
  • Contact: LI Hai-rong E-mail:lihairong20030829@163.com

Abstract:

Objective To explore the contribution of bone morphogenetic protein-2 (BMP-2) in the development of the cardiac outflow tract(OFT) of the mouse embryo.
Methods Serial paraffin sections of mouse embryonic hearts from embryonic day 9(E9) to E15 were stained with antibodies against α-sarcomeric actin(α-SCA), islet-1(ISL-1), proliferating cell nuclear antigen(PCNA) or BMP-2 by the immunohistochemical method. Three to seven mice were examined for each stage. Results At E9, no cell was observed in the cardiac jelly of OFT. Scarce PCNA expressing cells were found in OFT myocardium. Weak BMP-2 expressed in the OFT myocardium, endocardium and dorsal pericardium. During E9-11, with the addition of cardiomyocytes derived from the second heart field to the arterial pole, the OFT lengthened. The proliferation rate of these newly added cells dropped gradually during recruitment into the OFT. During E10-11, mesenchymal cells gradually filled the OFT ridges, some of them expressing BMP-2, PCNA. BMP-2 expression in myocardium of OFT was up-regulated to the peak at the stages and tapered off toward the poles, reaching up to the reflection of pericardium at the arterial pole. At E12, the OFT shortened and its BMP-2 expression level was down-regulated. During E13-15, the mesenchymal outlet septum were gradually myocardialized and weak BMP-2 expression was restricted to the OFT myocardium adjacent to the great vessels. During E10~13, myocardium of the distal OFT showed low proliferation activity while myocardium of the proximal OFT and right ventricle proliferated into trabeculae and resulted in the development of right ventricle. Conclusion BMP-2 induceds the precursors from the second heart field to differentiate into cardiomyocytes and add to the arterial pole of the heart. BMP-2 is participated in the development of OFT ridges. BMP-2 inhibites cardiomyocytes of OFT proliferating and its down-regulation in the proximal portion reinitiated cardiomyocytes proliferating, which leads to the development of right ventricle and shortening of the OFT. Low level of BMP-2 might induce mesenchymal cells in OFT septum to differentiate into cardiomyocytes.

Key words: Embryo, Cardiac outflow tract, Bone morphogenetic protein-2, Proliferating cell nuclear antigen, Islet-1, Immunohistochemistry, Mouse