HAND2-mediated epithelial maintenance and integrity in cardiac outflow tract morphogenesis
HAND2-mediated epithelial maintenance and integrity in cardiac outflow tract morphogenesis
复制标题
HAND2介导的心脏流出道形态发生中的上皮维持和完整性
DOI：
10.1242/dev.177477
复制
发表时间：
2019
期刊：
影响因子：
4.6
通讯作者：
Yang Zhongzhou
中科院分区：
文献类型：
--
作者：
Xia Meng;Luo Wen;Jin Hengwei;Yang Zhongzhou
在胚胎发生过程中，上皮组织是器官发生的先决条件，特别是管状结构的建立。最近的研究提供了早期心脏发育中上皮形成的线索，但尚未系统地探索。在这里，我们发现HAND2蛋白在心包前背壁（aDPW）和流出道（OFT）的邻近过渡区（TZ）的心脏祖细胞中存在梯度。Hand2的缺失导致细胞在TZ中阻滞和积累，导致形态发生缺陷。尽管顶基底细胞极性未受影响，但在Hand2突变小鼠的TZ中，粘附体连接和细胞-基质粘附的关键上皮元件被破坏，表明上皮形成不良。RNA-seq分析显示收缩纤维和肌动蛋白细胞骨架的调节改变，影响心肌细胞分化。此外，我们已经确定Stars是由HAND2转录控制的。STARS促进肌动蛋白聚合，这对于锚定粘附分子以产生细胞粘附至关重要。因此，我们发现了HAND2在介导上皮维持和OFT形态发生完整性方面的新功能。此外，本研究还为了解心脏祖细胞对OFT发展的贡献提供了见解。摘要：利用ashf特异性HAND2缺失小鼠，揭示了HAND2在心脏早期发育过程中介导OFT上皮维持和OFT形态发生完整性中的新功能。
ABSTRACT During embryogenesis, epithelial organization is the prerequisite for organogenesis, in particular, for establishing the tubular structure. Recent studies provided hints about epithelial formation in early heart development, which has not been systemically explored. Here, we revealed a gradient of HAND2 protein in cardiac progenitors in the anterior dorsal pericardial wall (aDPW) and adjacent transition zone (TZ) in the outflow tract (OFT). Deletion of Hand2 caused cell arrest and accumulation in the TZ, leading to defective morphogenesis. Although apicobasal cell polarity was unaffected, the key epithelial elements of adherens junction and cell-matrix adhesion were disrupted in the TZ of Hand2 mutant mice, indicating poorly formed epithelium. RNA-seq analysis revealed altered regulation of the contractile fiber and actin cytoskeleton, which affected cardiomyocyte differentiation. Furthermore, we have identified Stars as being transcriptionally controlled by HAND2. STARS facilitates actin polymerization that is essential for anchoring the adhesive molecules to create cell adhesion. Thus, we have uncovered a new function of HAND2 in mediating epithelial maintenance and integrity in OFT morphogenesis. In addition, this study also provides insights for understanding cardiac progenitor contribution to OFT development. Summary: Using aSHF-specific Hand2-deletion mice, a new function is revealed for HAND2 in mediating OFT epithelial maintenance and integrity in OFT morphogenesis during early heart development.