Rahkonen Otto, Savontaus Mikko, Abdelwahid Eltyeb, Vuorio Eero, Jokinen Eero
Department of Medical Biochemistry and Molecular Biology, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland.
Histochem Cell Biol. 2003 Aug;120(2):103-10. doi: 10.1007/s00418-003-0549-9. Epub 2003 Jul 18.
A majority of congenital heart defects are due to abnormal development of the valves and membranous septa, i.e., connective tissue components of the heart. During development, an interesting feature of cardiac connective tissue is transient expression of collagens typical for cartilage. To better understand the role of these collagens in the heart, we have performed a systematic study on the temporospatial expression of type II and IX collagen isoforms during mouse heart development employing northern hybridization and RNase protection assay. The mRNAs for alpha1(II) and alpha1(IX) collagens were expressed transiently between embryonic days 10.5 and 14.5 in embryonic mouse heart. RNase protection assays revealed that for both transcripts the embryonic ("prechondrogenic") variants of the alternatively spliced mRNA isoforms dominated. Immunohistochemistry demonstrated that type IIA collagen and Sox9, its key transcriptional regulator, were expressed in the epithelial-mesenchymal areas of the developing heart, with partially overlapping patterns particularly in valvular and septal regions. In addition, Sox9 expression was detected widely in the developing heart. These observations support the hypothesis that cartilage collagens, especially the long isoform of type II collagen, participate in the morphogenesis of cardiac valves and septa.
大多数先天性心脏缺陷是由于心脏瓣膜和膜性间隔(即心脏的结缔组织成分)发育异常所致。在发育过程中,心脏结缔组织的一个有趣特征是出现软骨特有的胶原蛋白的短暂表达。为了更好地理解这些胶原蛋白在心脏中的作用,我们利用Northern杂交和核糖核酸酶保护分析,对小鼠心脏发育过程中II型和IX型胶原蛋白亚型的时空表达进行了系统研究。α1(II)和α1(IX)胶原蛋白的mRNA在胚胎小鼠心脏胚胎期第10.5天至14.5天之间短暂表达。核糖核酸酶保护分析显示,对于这两种转录本,可变剪接的mRNA亚型的胚胎(“软骨形成前”)变体占主导。免疫组织化学表明,IIA型胶原蛋白及其关键转录调节因子Sox9在发育中心脏的上皮-间充质区域表达,特别是在瓣膜和间隔区域有部分重叠模式。此外,在发育中心脏广泛检测到Sox9表达。这些观察结果支持了软骨胶原蛋白,尤其是II型胶原蛋白的长亚型参与心脏瓣膜和间隔形态发生的假说。