Wtip is required for proepicardial organ specification and cardiac left/right asymmetry in zebrafish.
Wtip is required for proepicardial organ specification and cardiac left/right asymmetry in zebrafish.
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DOI：
10.3892/mmr.2016.5550
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发表时间：
2016-09
影响因子：
3.4
通讯作者：
Obara T
中科院分区：
文献类型：
--
作者：
Powell R;Bubenshchikova E;Fukuyo Y;Hsu C;Lakiza O;Nomura H;Renfrew E;Garrity D;Obara T
Wilm's tumor 1 interacting protein（Wtip）是一种与Wilm's tumor protein（WT1）相互作用的蛋白。WT1在心脏的前心外膜器官（PE）中表达，小鼠和斑马鱼WT1敲除模型似乎缺乏PE。wtip在心脏中的作用还未被探索。在本研究中，我们表明，wtip的表达是相同的wt1a，tcf21，和tbx18阳性PE细胞，和Wtip蛋白定位于基体的PE细胞。我们提出的第一个遗传证据表明，Wtip信号与WT1是必不可少的PE规格在斑马鱼心脏。通过过度表达wtip mRNA，我们观察到PE标记物在心脏和咽弓区域的异位表达。此外，wtip基因敲除胚胎表现出心脏循环紊乱，缺乏房室（AV）边界。然而，室特异性标记物amhc和vmhc不受影响。有趣的是，wtip的敲除会破坏早期的左右（LR）不对称性。我们的研究揭示了Wtip调节PE细胞特异性和早期LR不对称性的新作用，并表明PE可能对心脏循环和AV形态发生产生非自主作用。纤毛在PE中的存在，以及Wtip在纤毛细胞基体中的定位，提高了胚胎心脏中纤毛介导的PE信号传导的可能性。
Wilm's tumor 1 interacting protein (Wtip) was identified as an interacting partner of Wilm's tumor protein (WT1) in a yeast two-hybrid screen. WT1 is expressed in the proepicardial organ (PE) of the heart, and mouse and zebrafish wt1 knockout models appear to lack the PE. Wtip's role in the heart remains unexplored. In the present study, we demonstrate that wtip expression is identical in wt1a-, tcf21-, and tbx18-positive PE cells, and that Wtip protein localizes to the basal body of PE cells. We present the first genetic evidence that Wtip signaling in conjunction with WT1 is essential for PE specification in the zebrafish heart. By overexpressing wtip mRNA, we observed ectopic expression of PE markers in the cardiac and pharyngeal arch regions. Furthermore, wtip knockdown embryos showed perturbed cardiac looping and lacked the atrioventricular (AV) boundary. However, the chamber-specific markers amhc and vmhc were unaffected. Interestingly, knockdown of wtip disrupts early left-right (LR) asymmetry. Our studies uncover new roles for Wtip regulating PE cell specification and early LR asymmetry, and suggest that the PE may exert non-autonomous effects on heart looping and AV morphogenesis. The presence of cilia in the PE, and localization of Wtip in the basal body of ciliated cells, raises the possibility of cilia-mediated PE signaling in the embryonic heart.