A Conserved Role of the Unconventional Myosin 1d in Laterality Determination

A Conserved Role of the Unconventional Myosin 1d in Laterality Determination
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非常规肌球蛋白 1d 在偏侧性测定中的保守作用

DOI:
10.1016/j.cub.2018.01.075
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发表时间:
2018
期刊:
影响因子:
9.2
通讯作者:
Noselli
Noselli
中科院分区:
生物学1区
文献类型:
--
作者:
Tingler;Maerker;Schweickert;LeBlanc Straceski;Noselli

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解剖和功能的不对称性在动物界中广泛存在[1,2]。在脊椎动物中,许多内脏器官是不对称放置的[3]。蜗牛的壳和内部器官是不对称卷曲的,果蝇的生殖器和后肠在发育过程中经历手性旋转。这些不对称性的进化起源仍然是一个悬而未决的问题[1]。节点信号被广泛使用[4],许多但不是所有的脊椎动物使用纤毛来对称破缺[5]。在缺乏纤毛和Nodal的果蝇中,非常规的肌球蛋白ID(myo 1d)基因控制手性器官的右旋[6,7]。在这里,我们研究了Myo 1 in左-右(LR)轴形成在爪蟾中的作用。Morpholino寡聚体介导的myo 1d下调影响了>50%的morphant蝌蚪的器官放置。在>70%的病例中,左不对称Nodal级联的诱导是异常的。由于LR组织者的纤毛更短、更少和非极化,血流靶基因5的表达受到损害,血流本身也是如此。其他表型精确定位了Wnt/平面细胞极性信号传导,并表明myo 1d与果蝇[8]一样,在平面细胞极性通路的背景下起作用。事实上,在myo 1dmorphants中,原肠胚外植体培养物的会聚延伸被抑制,非经典Wnt信号的ATF 2报告基因被下调。最后,遗传干扰实验证明了核心平面细胞极性信号转导基因12和myo 1din LR轴形成之间的功能性相互作用。因此,我们的数据identifiedmyo 1作为节肢动物和脊索动物的不对称性的共同点,与动物不对称性的单系起源一致。
Anatomical and functional asymmetries are widespread in the animal kingdom [1, 2]. In vertebrates, many visceral organs are asymmetrically placed [3]. In snails, shells and inner organs coil asymmetrically, and inDrosophila, genitalia and hindgut undergo a chiral rotation during development. The evolutionary origin of these asymmetries remains an open question [1]. Nodal signaling is widely used [4], and many, but not all, vertebrates use cilia for symmetry breaking [5]. InDrosophila, which lacks both cilia and Nodal, the unconventionalmyosin ID(myo1d) gene controls dextral rotation of chiral organs [6, 7]. Here, we studied the role ofmyo1din left-right (LR) axis formation inXenopus. Morpholino oligomer-mediatedmyo1ddownregulation affected organ placement in >50% of morphant tadpoles. Induction of the left-asymmetric Nodal cascade was aberrant in >70% of cases. Expression of the flow-target genedand5was compromised, as was flow itself, due to shorter, fewer, and non-polarized cilia at the LR organizer. Additional phenotypes pinpointed Wnt/planar cell polarity signaling and suggested thatmyo1d, like inDrosophila[8], acted in the context of the planar cell polarity pathway. Indeed, convergent extension of gastrula explant cultures was inhibited inmyo1dmorphants, and theATF2reporter gene for non-canonical Wnt signaling was downregulated. Finally, genetic interference experiments demonstrated a functional interaction between the core planar cell polarity signaling genevangl2andmyo1din LR axis formation. Thus, our data identifiedmyo1das a common denominator of arthropod and chordate asymmetry, in agreement with a monophyletic origin of animal asymmetry.
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