Master of Science in Integrative Biology Program, Kennesaw State University, USA; Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA, 30144, USA.
Department of Molecular and Cellular Biology, Kennesaw State University, Kennesaw, GA, 30144, USA.
Dev Biol. 2021 Jan 1;469:1-11. doi: 10.1016/j.ydbio.2020.09.001. Epub 2020 Sep 17.
The regulation of formation of the Drosophila heart by the Nkx 2.5 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.
果蝇心脏的形成受 Nkx 2.5 同源物 Tinman 的调节，这是胚胎发育过程中的一个关键事件。在这项研究中，我们确定了高度保守的转录共激活因子 Akirin 是 Twist 转录共激活因子最早诱导 tinman 的关键因素。akirin 突变体胚胎在心脏中表现出多种形态缺陷，包括主动脉细胞行之间的间距异常和主动脉流出道的异常模式。akirin 突变体胚胎中的 tinman 转录本水平大大降低，同时在心脏模式形成的最早阶段 Tinman 蛋白减少。此外，akirin 突变体中的 Tinman 阳性心肌细胞数量减少，伴随心脏的模式和组织紊乱。最后，尽管在 akirin 突变体中明显形成了心脏，但与野生型心脏相比，这些突变体心脏的协调收缩较少。这些结果表明，Akirin 对于 Twist 转录因子对 tinman 的最初诱导至关重要，并且心脏模式形成程序的成功高度依赖于在心脏发育途径的最早步骤中建立适当的 tinman 水平。
