Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom.
Department of Infection, Immunity and Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
PLoS One. 2021 Nov 30;16(11):e0260372. doi: 10.1371/journal.pone.0260372. eCollection 2021.
Collective cell migration is essential for embryonic development and homeostatic processes. During zebrafish development, the posterior lateral line primordium (pLLP) navigates along the embryo flank by collective cell migration. The chemokine receptors, Cxcr4b and Cxcr7b, as well as their cognate ligand, Cxcl12a, are essential for this process. We corroborate that knockdown of the zebrafish cd9 tetraspanin orthologue, cd9b, results in mild pLL abnormalities. Through generation of CRISPR and TALEN mutants, we show that cd9a and cd9b function partially redundantly in pLLP migration, which is delayed in the cd9b single and cd9a; cd9b double mutants. This delay led to a transient reduction in neuromast numbers. Loss of both Cd9a and Cd9b sensitized embryos to reduced Cxcr4b and Cxcl12a levels. Together these results provide evidence that Cd9 modulates collective cell migration of the pLLP during zebrafish development. One interpretation of these observations is that Cd9 contributes to more effective chemokine signalling.
细胞集体迁移对于胚胎发育和体内平衡过程至关重要。在斑马鱼胚胎发育过程中，后侧线原基（pLLP）通过细胞集体迁移沿着胚胎侧翼移动。趋化因子受体 Cxcr4b 和 Cxcr7b 及其同源配体 Cxcl12a 对于这一过程至关重要。我们证实，斑马鱼 tetraspanin 同源物 cd9b 的敲低会导致 pLL 轻度异常。通过生成 CRISPR 和 TALEN 突变体，我们表明 cd9a 和 cd9b 在 pLLP 迁移中部分冗余，cd9b 单突变体和 cd9a;cd9b 双突变体中的迁移过程会被延迟。这种延迟导致神经节数量暂时减少。Cd9a 和 Cd9b 的缺失均使胚胎对 Cxcr4b 和 Cxcl12a 水平降低更为敏感。这些结果共同提供了证据表明 Cd9 调节斑马鱼发育过程中 pLLP 的细胞集体迁移。对这些观察结果的一种解释是，Cd9 有助于更有效的趋化因子信号传导。
