Akirin is critical for early tinman induction and subsequent formation of the heart in Drosophila melanogaster.

Akirin is critical for early tinman induction and subsequent formation of the heart in Drosophila melanogaster.
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DOI:
10.1016/j.ydbio.2020.09.001
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发表时间:
2021-01-01
影响因子:
2.7
通讯作者:
Nowak SJ
Nowak SJ
中科院分区:
生物学3区
文献类型:
--
作者:
Howard AM;Milner H;Hupp M;Willett C;Palermino K;Nowak SJ

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Nkx2.5同源基因Tinman对果蝇心脏形成的调控是胚胎发育过程中的一个关键事件。在本研究中,我们发现高度保守的转录辅助因子Akirin是Twist转录辅助因子最早诱导tinman的关键因子。Akirin突变胚胎在心脏中表现出各种形态缺陷,包括主动脉细胞行间距异常和主动脉流出道模式异常。akirin突变胚胎的tinman转录本水平大大降低,同时在心脏模式形成的早期阶段tinman蛋白也减少。此外,akirin突变减少了tinman阳性心肌细胞的数量,并伴有心脏的模式和组织的破坏。最后,尽管在akirin突变体中心脏明显形成,但与野生型心脏相比,这些突变心脏在akirin突变体中表现出更少的协调收缩。这些结果表明,Akirin对于Twist转录因子首次诱导tinman至关重要,并且心脏模式程序的成功高度依赖于在心脏发育途径的早期阶段建立适当水平的tinman。
The regulation of formation of the Drosophila heart by the Nkx2.5 homologue Tinman is a key event during embryonic development. In this study, we identify the highly conserved transcription cofactor Akirin as a key factor in the earliest induction of tinman by the Twist transcription cofactor. akirin mutant embryos display a variety of morphological defects in the heart, including abnormal spacing between rows of aortic cells and abnormal patterning of the aortic outflow tract. akirin mutant embryos have a greatly reduced level of tinman transcripts, together with a reduction of Tinman protein in the earliest stages of cardiac patterning. Further, akirin mutants have reduced numbers of Tinman-positive cardiomyoblasts, concomitant with disrupted patterning and organization of the heart. Finally, despite the apparent formation of the heart in akirin mutants, these mutant hearts exhibit fewer coordinated contractions in akirin mutants compared with wild-type hearts. These results indicate that Akirin is crucial for the first induction of tinman by the Twist transcription factor, and that the success of the cardiac patterning program is highly dependent upon establishing the proper level of tinman at the earliest steps of the cardiac developmental pathway.
akirin是减数分裂前期 I 的二分裂二价结构和突触复合体解体所必需的。
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