Mich John K, Blaser Heiko, Thomas Natalie A, Firestone Ari J, Yelon Deborah, Raz Erez, Chen James K
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
Dev Biol. 2009 Apr 15;328(2):342-54. doi: 10.1016/j.ydbio.2009.01.036. Epub 2009 Feb 4.
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.
原始生殖细胞（PGCs）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。先前的报道表明，刺猬蛋白（Hh）在果蝇胚胎中作为PGC迁移的化学引诱剂，并且下游信号蛋白如 patched（Ptc）和 smoothened（Smo）是PGC定位于体细胞性腺前体所必需的。在这里，我们以斑马鱼为模型系统，研究Hh信号是否是脊椎动物PGC迁移所必需的。我们发现，环杷明，一种Hh信号的抑制剂，会导致斑马鱼胚胎中PGC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；相反，我们发现母源和合子的Smo对于斑马鱼胚胎中的PGC迁移都不是必需的。环杷明反而独立于Smo发挥作用，部分通过失调细胞黏附以及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，Hh信号不是斑马鱼PGC迁移所必需的，并强调了体内细胞迁移中调节细胞间黏附的重要性。
