Casarosa Simona, Amato Marcos A, Andreazzoli Massimiliano, Gestri Gaia, Barsacchi Giuseppina, Cremisi Federico
Sezione di Biologia Cellulare e dello Sviluppo, Dipartimento di Fisiologia e Biochimica, Università di Pisa, via Carducci 13-56010 Ghezzano (Pisa), Italy.
Mol Cell Neurosci. 2003 Jan;22(1):25-36. doi: 10.1016/s1044-7431(02)00025-8.
We investigated the function of Xrx1 during Xenopus retinogenesis. Xrx1 overexpression lengthens mitotic activity and ectopically activates the expression of markers of undifferentiated progenitors in the developing retina. We assayed Xrx1 ability to support proliferation with a cell-autonomous mechanism by in vivo lipofection of single retinal progenitors. Xrx1 overexpression increases clonal proliferation while Xrx1 functional inactivation exerts the opposite effect. We also compared the effects of Xrx1 with those of the cyclin-dependent kinase cdk2, a strong mitotic promoter. Despite the similar increase in clonal proliferation displayed by both factors, Xrx1 and cdk2 act differently on retinal cell fate determination. cdk2/cyclinA2 lipofected retinas show a decrease in early-born cell types as ganglion cells and cones and an increase in late-born types such as bipolar neurons. On the contrary, Xrx1 lipofected retinas show no changes in the proportions of the different cell types, thus suggesting a role in supporting multipotency of retinal progenitors.
我们研究了Xrx1在非洲爪蟾视网膜发育过程中的功能。Xrx1的过表达延长了有丝分裂活性，并异位激活了发育中视网膜中未分化祖细胞标志物的表达。我们通过对单个视网膜祖细胞进行体内脂质转染，以细胞自主机制检测Xrx1支持增殖的能力。Xrx1的过表达增加了克隆增殖，而Xrx1的功能失活则产生相反的效果。我们还比较了Xrx1与细胞周期蛋白依赖性激酶cdk2（一种强大的有丝分裂促进剂）的作用效果。尽管这两种因子都表现出类似的克隆增殖增加，但Xrx1和cdk2在视网膜细胞命运决定上的作用方式不同。脂质转染cdk2/cyclinA2的视网膜中，早期生成的细胞类型如神经节细胞和视锥细胞减少，而晚期生成的细胞类型如双极神经元增加。相反地，脂质转染Xrx1的视网膜中不同细胞类型的比例没有变化，因此表明其在支持视网膜祖细胞多能性方面发挥作用。
