Tang Min, Yuan Wuzhou, Bodmer Rolf, Wu Xiushan, Ocorr Karen
The Center for Heart Development, Key Laboratory of MOE for Developmental Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, People's Republic of China; Development and Aging Program, Sanford-Burnham Medical Research Institute, La Jolla, California, 92037.
Genesis. 2014 Jan;52(1):19-28. doi: 10.1002/dvg.22724. Epub 2013 Nov 21.
Cardiac valves serve an important function; they support unidirectional blood flow and prevent blood regurgitation. Wnt signaling plays an important role in the formation of mouse cardiac valves and cardiac valve proliferation in Zebrafish, but identification of the specific signaling components involved has not been addressed systematically. Of the components involved in Wnt signal transduction, pygopus (pygo), first identified as a core component of Wnt signaling in Drosophila, has not yet to be investigated with respect to valve development and differentiation. Here, we take advantage of the Drosophila heart model to study the role of pygo in formation of valves between the cardiac chambers. We found that cardiac-specific pygo knockdown in the Drosophila heart causes dilation in the region of these cardiac valves, and their characteristic dense mesh of myofibrils does not form and resembles that of neighboring cardiomyocytes. In contrast, heart-specific knockdown of the transcription factors, arm/β-Cat, lgs/BCL9, or pan/TCF, which mediates canonical Wnt signal transduction, shows a much weaker valve differentiation defect. Double-heterozygous combinations of mutants for pygo and the Wnt-signaling components have no additional effect on heart function compared with pygo heterozygotes alone. These results are consistent with the idea that pygo functions independently of canonical Wnt signaling in the differentiation of the adult interchamber cardiac valves.
心脏瓣膜发挥着重要作用；它们支持血液单向流动并防止血液反流。Wnt信号通路在小鼠心脏瓣膜形成和斑马鱼心脏瓣膜增殖过程中发挥重要作用，但尚未系统地鉴定其中涉及的特定信号成分。在参与Wnt信号转导的成分中，pygopus（pygo）最初在果蝇中被鉴定为Wnt信号通路的核心成分，但其在瓣膜发育和分化方面尚未得到研究。在这里，我们利用果蝇心脏模型来研究pygo在心脏腔室间瓣膜形成中的作用。我们发现，果蝇心脏中特异性敲低pygo会导致这些心脏瓣膜区域扩张，并且其特征性的致密肌原纤维网无法形成，类似于相邻心肌细胞的肌原纤维网。相比之下，介导经典Wnt信号转导的转录因子arm/β-Cat、lgs/BCL9或pan/TCF在心脏中特异性敲低时，瓣膜分化缺陷要弱得多。与单独的pygo杂合子相比，pygo与Wnt信号成分的双杂合突变体组合对心脏功能没有额外影响。这些结果与以下观点一致，即pygo在成人间腔室心脏瓣膜的分化中独立于经典Wnt信号通路发挥作用。
