dmrt2 and myf5 Link Early Somitogenesis to Left-Right Axis Determination in Xenopus laevis.
dmrt2 and myf5 Link Early Somitogenesis to Left-Right Axis Determination in Xenopus laevis.
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DOI：
10.3389/fcell.2022.858272
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发表时间：
2022
影响因子：
5.5
通讯作者：
Schweickert, Axel
中科院分区：
文献类型：
--
作者：
Tingler, Melanie;Brugger, Amelie;Feistel, Kerstin;Schweickert, Axel
脊椎动物的左右轴在神经形成期间由一种被称为左-右组织器(LRO)的瞬时纤毛上皮中发生的事件指定，该上皮由两种不同的细胞类型组成。在中轴线，中央LRO(CLRO)细胞投射出活动的单纤毛，并产生向左的流体流动，这代表了对称性破坏的机制。这种定向的流体流动是由横向定位的感觉LRO(SLRO)细胞感受到的，这些细胞含有不活动的纤毛。在左侧的sLRO细胞中，流诱导的信号触发多途径拮抗剂Dand5的转录后抑制。随后，共表达的转化生长因子-β生长因子Nodal1从Dand5介导的抑制中释放出来，诱导左侧基因表达。有趣的是，非洲爪哇的sLRO细胞具有体细胞命运，这表明LR决定和体细胞发生之间存在联系。在这里，我们证明了双重性别和mab3相关的转录因子2(Dmrt2)，已知参与脊椎动物的体细胞发生，是LRO纤毛发生和sLRO规范所必需的。在dmrt2变异体中，原肠胚早期的肌源性转录因子tbx6和myf5的错误表达先于神经胚期的sLRO细胞的错误指定。由于sLRO发育失败，myf5变种蝌蚪也显示出LR缺陷。Myf5功能的获得将sLRO细胞重新引入到dmrt2变异体中，表明在非洲爪哇中，旁轴构图和体细胞发生在功能上与LR轴的形成有关。
The vertebrate left-right axis is specified during neurulation by events occurring in a transient ciliated epithelium termed left-right organizer (LRO), which is made up of two distinct cell types. In the axial midline, central LRO (cLRO) cells project motile monocilia and generate a leftward fluid flow, which represents the mechanism of symmetry breakage. This directional fluid flow is perceived by laterally positioned sensory LRO (sLRO) cells, which harbor non-motile cilia. In sLRO cells on the left side, flow-induced signaling triggers post-transcriptional repression of the multi-pathway antagonist dand5. Subsequently, the co-expressed Tgf-β growth factor Nodal1 is released from Dand5-mediated repression to induce left-sided gene expression. Interestingly, Xenopus sLRO cells have somitic fate, suggesting a connection between LR determination and somitogenesis. Here, we show that doublesex and mab3-related transcription factor 2 (Dmrt2), known to be involved in vertebrate somitogenesis, is required for LRO ciliogenesis and sLRO specification. In dmrt2 morphants, misexpression of the myogenic transcription factors tbx6 and myf5 at early gastrula stages preceded the misspecification of sLRO cells at neurula stages. myf5 morphant tadpoles also showed LR defects due to a failure of sLRO development. The gain of myf5 function reintroduced sLRO cells in dmrt2 morphants, demonstrating that paraxial patterning and somitogenesis are functionally linked to LR axis formation in Xenopus.
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