Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai, 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai, 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
Differentiation. 2019 Jan-Feb;105:71-79. doi: 10.1016/j.diff.2019.02.001. Epub 2019 Feb 8.
Cell migration in response to morphogen gradients affects morphogenesis. Chemotaxis towards adenosine 3', 5'-monophosphate (cAMP) is essential for the early stage of morphogenesis in the slime mold Dictyostelium discoideum. Here, we show that D. discoideum completes morphogenesis without cAMP-chemotaxis-dependent cell migration. The extracellular cAMP gradient is believed to cause cells to form a slug-shaped multicellular structure and fruiting body. The cAMP receptor, cAR1, was not expressed at the cell surface during these stages, correlating with reduced chemotactic activity. Gβ-null cells expressing temperature sensitive Gβ are unable to generate extracellular cAMP (Jin et al., 1998) and thus unable to aggregate and exhibit proper morphogenesis under restrictive temperature. However, when mixed with wild type cells ts-Gβ expressing gβ-null cells normally aggregated and exhibited normal morphogenesis under restrictive temperature. Furthermore, cells migrated after aggregation in a mixture containing wild-type cells. KI-5 cells, which do not show aggregation or morphogenesis, spontaneously migrated to a transplanted wild-type tip and underwent normal morphogenesis and cell differentiation; this was not observed in cells lacking tgrB1and tgrC1 cells adhesion molecules. Thus, cAMP gradient-dependent cell migration may not be required for multicellular pattern formation in late Dictyostelium development.
细胞对形态发生梯度的迁移反应会影响形态发生。向腺苷 3',5'-单磷酸(cAMP)的趋化作用对于变形虫 D. discoideum 的形态发生早期阶段是必不可少的。在这里,我们表明 D. discoideum 可以在没有 cAMP-趋化性依赖性细胞迁移的情况下完成形态发生。据信细胞外 cAMP 梯度会导致细胞形成类似于鼻涕虫形状的多细胞结构和子实体。在这些阶段,cAMP 受体 cAR1 没有在细胞表面表达,与趋化活性降低相关。表达温度敏感 Gβ 的 Gβ-缺失细胞无法产生细胞外 cAMP(Jin 等人,1998),因此在限制温度下无法聚集并表现出适当的形态发生。然而,当与野生型细胞混合时,ts-Gβ 表达 gβ-缺失细胞在限制温度下正常聚集并表现出正常的形态发生。此外,在包含野生型细胞的混合物中聚集后,细胞发生迁移。不表现出聚集或形态发生的 KI-5 细胞会自发迁移到移植的野生型尖端,并经历正常的形态发生和细胞分化;在缺乏 tgrB1 和 tgrC1 细胞粘附分子的细胞中没有观察到这种情况。因此,cAMP 梯度依赖性细胞迁移可能不是晚期 Dictyostelium 发育中多细胞模式形成所必需的。