Bota Catarina, Martins Gabriel G, Lopes Susana S
iNOVA4Health, NOVA Medical School Faculdade de Ciências Médicas, NMS|FCM, Universidade Nova de Lisboa, Lisboa, Portugal.
Instituto Gulbenkian de Ciência, Fundação Calouste Gulbenkian, Oeiras, Portugal.
Front Cell Dev Biol. 2023 Jan 9;10:989615. doi: 10.3389/fcell.2022.989615. eCollection 2022.
During vertebrate development, symmetry breaking occurs in the left-right organizer (LRO). The transfer of asymmetric molecular information to the lateral plate mesoderm is essential for the precise patterning of asymmetric internal organs, such as the heart. However, at the same developmental time, it is crucial to maintain symmetry at the somite level for correct musculature and vertebrae specification. We demonstrate how left-right signals affect the behavior of zebrafish somite cell precursors by using live imaging and fate mapping studies in dand5 homozygous mutants compared to wildtype embryos. We describe a population of cells in the vicinity of the LRO, named Non-KV Sox17:GFP+ Tailbud Cells (NKSTCs), which migrate anteriorly and contribute to future somites. We show that NKSTCs originate in a cluster of cells aligned with the midline, posterior to the LRO, and leave that cluster in a left-right alternating manner, primarily from the left side. Fate mapping revealed that more NKSTCs integrated somites on the left side of the embryo. We then abolished the asymmetric cues from the LRO using dand5-/- mutant embryos and verified that NKSTCs no longer displayed asymmetric patterns. Cell exit from the posterior cluster became bilaterally synchronous in dand5-/- mutants. Our study revealed a new link between somite specification and Dand5 function. The gene dand5 is well known as the first asymmetric gene involved in vertebrate LR development. This study revealed a new link for Dand5 as a player in cell exit from the maturation zone into the presomitic mesoderm, affecting the expression patterns of myogenic factors and tail size.
在脊椎动物发育过程中，左右不对称性的打破发生在左右组织者（LRO）中。将不对称分子信息传递到侧板中胚层对于不对称内部器官（如心脏）的精确模式形成至关重要。然而，在相同的发育时期，在体节水平维持对称性对于正确的肌肉组织和椎骨特化至关重要。我们通过在dand5纯合突变体与野生型胚胎中使用实时成像和命运图谱研究，展示了左右信号如何影响斑马鱼体节细胞前体的行为。我们描述了LRO附近的一群细胞，命名为非Kupffer囊泡Sox17：GFP +尾芽细胞（NKSTCs），它们向前迁移并对未来的体节做出贡献。我们表明，NKSTCs起源于与中线对齐的一群细胞，位于LRO后方，并以左右交替的方式离开该群体，主要从左侧离开。命运图谱显示，更多的NKSTCs整合到胚胎左侧的体节中。然后，我们使用dand5-/-突变体胚胎消除了来自LRO的不对称线索，并验证NKSTCs不再显示不对称模式。在dand5-/-突变体中，细胞从后群体的退出变得双侧同步。我们的研究揭示了体节特化与Dand5功能之间的新联系。基因dand5是脊椎动物左右发育中涉及的第一个不对称基因，广为人知。这项研究揭示了Dand5作为细胞从成熟区进入前体节中胚层的参与者的新联系，影响了生肌因子的表达模式和尾巴大小。
