Di Carlo A, De Felici M
Department of Public Health and Cell Biology, University of Rome "Tor Vergata,", Rome, 00133, Italy.
Dev Biol. 2000 Oct 15;226(2):209-19. doi: 10.1006/dbio.2000.9861.
In this study we show that mouse primordial germ cells and fetal germ cells at certain stages of differentiation express E-cadherin and alpha and beta catenins. Moreover, we demonstrate that the formation of germ cell aggregates that rapidly occurs when monodispersed germ cell populations are released from embryonic gonads in culture is E-cadherin mediated, developmentally regulated, and dependent on the sex of the germ cells. Immunoblotting analyses indicate that the lower ability to form aggregates of primordial germ cells in comparison to fetal germ cells is not due to gross changes in E-cadherin expression, altered association with beta catenin, or changes in beta catenin phosphorylation. Investigating possible functions of E-cadherin-mediated adhesion in primordial germ cell development, we found that E-cadherin-mediated adhesion may stimulate the motility of primordial germ cells. Moreover, treatment of primordial germ cells cultured on STO cell monolayers with an anti-E-cadherin antibody caused a significant decrease in their number and markedly reduced their ability to form colonies in vitro. The same in vitro treatment of explanted undifferentiated gonadal ridges cultured for 4 days results in decreased numbers and altered localization of the germ cell inside the gonads. Taken together these results suggest that E-cadherin plays an important role in primordial germ cell migration and homing and may act as a modulator of primordial germ cell development.
在本研究中,我们发现小鼠原始生殖细胞和处于特定分化阶段的胎儿生殖细胞表达E-钙黏蛋白以及α和β连环蛋白。此外,我们证明,当在培养中从胚胎性腺释放单分散的生殖细胞群体时迅速发生的生殖细胞聚集体的形成是由E-钙黏蛋白介导的、受发育调控的,并且取决于生殖细胞的性别。免疫印迹分析表明,与胎儿生殖细胞相比,原始生殖细胞形成聚集体的能力较低并非由于E-钙黏蛋白表达的总体变化、与β连环蛋白的结合改变或β连环蛋白磷酸化的变化。在研究E-钙黏蛋白介导的黏附在原始生殖细胞发育中的可能功能时,我们发现E-钙黏蛋白介导的黏附可能刺激原始生殖细胞的运动。此外,用抗E-钙黏蛋白抗体处理在STO细胞单层上培养的原始生殖细胞,导致其数量显著减少,并明显降低其在体外形成集落的能力。对培养4天的外植未分化性腺嵴进行相同的体外处理,导致性腺内生殖细胞数量减少且定位改变。综合这些结果表明,E-钙黏蛋白在原始生殖细胞迁移和归巢中起重要作用,并且可能作为原始生殖细胞发育的调节因子。