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Conservation as well as divergence in Mcidas function underlies the differentiation of multiciliated cells in vertebrates.
Developmental Biology ( IF 2.7 ) Pub Date : 2020-07-28 , DOI: 10.1016/j.ydbio.2020.07.005
Feng Zhou 1 , Dheeraj Rayamajhi 2 , Vydianathan Ravi 1 , Vijay Narasimhan 1 , Yan Ling Chong 1 , Hao Lu 1 , Byrappa Venkatesh 3 , Sudipto Roy 4
Affiliation  

Multiciliated cells (MCCs) differentiate hundreds of motile cilia that beat to drive fluid movement over various kinds of epithelia. In Xenopus, mice and human, the coiled-coil containing protein Mcidas (Mci) has been shown to be a key transcriptional regulator of MCC differentiation. We have examined Mci function in the zebrafish, another model organism that is widely used to study ciliary biology. We show that zebrafish mci is expressed specifically in the developing MCCs of the kidney tubules, but surprisingly, not in those of the nasal placodes. Mci proteins lack a DNA binding domain and associate with the cell-cycle transcription factors E2f4/5 for regulating MCC-specific gene expression. We found that while the zebrafish Mci protein can complex with the E2f family members, its sequence as well as the requirement and sufficiency for MCC differentiation has diverged significantly from Mci homologues of the tetrapods. We also provide evidence that compared to Gmnc, another related coiled-coil protein that has recently been shown to regulate MCC development upstream of Mci, the Mci protein originated later within the vertebrate lineage. Based on these data, we argue that in contrast to Gmnc, which has a vital role in the genetic circuitry that drives MCC formation, the requirement of Mci, at least in the zebrafish, is not obligatory.



中文翻译:

Mcidas功能的保守性和差异性是脊椎动物多纤毛细胞分化的基础。

多纤毛细胞(MCCs)分化了数百个运动性纤毛,这些纤毛跳动以驱动流体在各种上皮细胞上运动。在非洲爪蟾,小鼠和人类中,含卷曲螺旋蛋白Mcidas(Mci)已被证明是MCC分化的关键转录调节因子。我们已经检查了斑马鱼中的Mci功能,这是另一种广泛用于研究睫状生物学的模型生物。我们展示了斑马鱼mci在肾小管的MCCs中特异性地表达“鼻咽癌”,但是令人惊讶的是,在鼻中膜中没有表达。Mci蛋白缺乏DNA结合结构域,并与细胞周期转录因子E2f4 / 5结合以调节MCC特异性基因表达。我们发现,虽然斑马鱼的Mci蛋白可以与E2f家族成员形成复合体,但其序列以及MCC分化的要求和充分性已与四足动物的Mci同源物显着不同。我们还提供了证据,与最近被证明可调节Mci上游MCC发育的另一种相关卷曲螺旋蛋白Gmnc相比,Mci蛋白起源于脊椎动物谱系。根据这些数据,我们认为与Gmnc相反,后者在驱动MCC形成的遗传电路中起着至关重要的作用,

更新日期:2020-07-28
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