Bussmann Jeroen, Bakkers Jeroen, Schulte-Merker Stefan
Hubrecht Institute, Utrecht, The Netherlands.
PLoS Genet. 2007 Aug;3(8):e140. doi: 10.1371/journal.pgen.0030140. Epub 2007 Jul 9.
The primitive heart tube is composed of an outer myocardial and an inner endocardial layer that will give rise to the cardiac valves and septa. Specification and differentiation of these two cell layers are among the earliest events in heart development, but the embryonic origins and genetic regulation of early endocardial development remain largely undefined. We have analyzed early endocardial development in the zebrafish using time-lapse confocal microscopy and show that the endocardium seems to originate from a region in the lateral plate mesoderm that will give rise to hematopoietic cells of the primitive myeloid lineage. Endocardial precursors appear to rapidly migrate to the site of heart tube formation, where they arrive prior to the bilateral myocardial primordia. Analysis of a newly discovered zebrafish Scl/Tal1 mutant showed an additional and previously undescribed role of this transcription factor during the development of the endocardium. In Scl/Tal1 mutant embryos, endocardial precursors are specified, but migration is severely defective and endocardial cells aggregate at the ventricular pole of the heart. We further show that the initial fusion of the bilateral myocardial precursor populations occurs independently of the endocardium and tal1 function. Our results suggest early separation of the two components of the primitive heart tube and imply Scl/Tal1 as an indispensable component of the molecular hierarchy that controls endocardium morphogenesis.
原始心管由外层心肌层和内层心内膜层组成，这两层将发育为心脏瓣膜和间隔。这两层细胞的特化和分化是心脏发育中最早发生的事件之一，但早期心内膜发育的胚胎起源和基因调控在很大程度上仍不明确。我们利用延时共聚焦显微镜分析了斑马鱼早期的心内膜发育，结果显示心内膜似乎起源于侧板中胚层的一个区域，该区域将发育为原始髓系谱系的造血细胞。心内膜前体细胞似乎迅速迁移到心管形成的部位，它们比双侧心肌原基更早到达此处。对新发现的斑马鱼Scl/Tal1突变体的分析表明，这种转录因子在心脏内膜发育过程中具有额外的、此前未被描述的作用。在Scl/Tal1突变体胚胎中，心内膜前体细胞已经特化，但迁移存在严重缺陷，心内膜细胞聚集在心脏的心室极。我们进一步表明，双侧心肌前体细胞群的初始融合独立于心内膜和tal1功能发生。我们的结果提示原始心管的两个组成部分在早期是分离的，并表明Scl/Tal1是控制心内膜形态发生的分子层级中不可或缺的组成部分。
