Germ cell migration in zebrafish is cyclopamine-sensitive but Smoothened-independent.
Germ cell migration in zebrafish is cyclopamine-sensitive but Smoothened-independent.
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DOI：
10.1016/j.ydbio.2009.01.036
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发表时间：
2009-04-15
影响因子：
2.7
通讯作者：
Chen, James K.
中科院分区：
文献类型：
--
作者：
Mich, John K.;Blaser, Heiko;Thomas, Natalie A.;Firestone, Ari J.;Yelon, Deborah;Raz, Erez;Chen, James K.
原始生殖细胞（PGC）是后生动物生殖细胞的祖细胞，是研究体内细胞迁移的重要模型。之前的报道表明，Hedgehog (Hh) 蛋白作为果蝇胚胎中 PGC 迁移的化学引诱剂，下游信号蛋白如 Patched (Ptc) 和 Smoothened (Smo) 是 PGC 定位到体细胞性腺前体所必需的。在这里，我们使用斑马鱼作为模型系统，探讨脊椎动物 PGC 迁移是否需要 Hh 信号传导。我们发现环巴明（Hh 信号传导抑制剂）会导致斑马鱼胚胎中 PGC 的迁移出现严重缺陷。然而，这些缺陷并不是由于环杷明对 Smoothened (Smo) 的抑制所致；相反，我们发现斑马鱼胚胎中 PGC 迁移既不需要母体 Smo，也不需要合子 Smo。相反，Cyclopamine 独立于 Smo 发挥作用，部分通过调节细胞粘附和解偶联细胞极化和易位来降低斑马鱼 PGC 的运动性。这些结果表明，斑马鱼 PGC 迁移不需要 Hh 信号传导，并强调了调节细胞-细胞粘附对于体内细胞迁移的重要性。
Primordial germ cells (PGCs) are the progenitors of reproductive cells in metazoans and are an important model for the study of cell migration in vivo. Previous reports have suggested that Hedgehog (Hh) protein acts as a chemoattractant for PGC migration in the Drosophila embryo and that downstream signaling proteins such as Patched (Ptc) and Smoothened (Smo) are required for PGC localization to somatic gonadal precursors. Here we interrogate whether Hh signaling is required for PGC migration in vertebrates, using the zebrafish as a model system. We find that cyclopamine, an inhibitor of Hh signaling, causes strong defects in the migration of PGCs in the zebrafish embryo. However, these defects are not due to inhibition of Smoothened (Smo) by cyclopamine; rather, we find that neither maternal nor zygotic Smo is required for PGC migration in the zebrafish embryo. Cyclopamine instead acts independently of Smo to decrease the motility of zebrafish PGCs, in part by dysregulating cell adhesion and uncoupling cell polarization and translocation. These results demonstrate that Hh signaling is not required for zebrafish PGC migration, and underscore the importance of regulated cell-cell adhesion for cell migration in vivo.
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影响因子：
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