Pimentel Angel C, Venkatesh Tadmiri R
Department of Biology, City College of New York and Graduate Center, J526, City University of New York, 138th Street and Convent Avenue, New York, NY 10031, USA.
Dev Biol. 2005 Sep 15;285(2):436-46. doi: 10.1016/j.ydbio.2005.07.011.
The rap (retina aberrant in pattern) gene encodes the Fizzy-related protein (Fzr), which as an activator of the ubiquitin ligase complex; APC/C (anaphase promoting complex/cyclosome) facilitates the cell cycle stage-specific degradation of cyclins. Loss-of-function mutations in rap cause unscheduled accumulation of cyclin B in the developing eye imaginal disc, resulting in additional mitotic cycles and defective patterning of the developing Drosophila eye. Targeted mis-expression of rap/fzr in the eye primordial cells causes precocious cell cycle exit, and smaller primordial eye fields, which either eliminate or drastically reduce the size of the adult eye. Although mitosis is inhibited in the mis-expression animals, cells with abnormally large nuclei form tumor-like structures from continued endoreplication, cell growth and retinal differentiation. Interestingly, overexpression of Rap/Fzr in the eye primordia also increases the size of the antennal primordium resulting in the induction of ectopic antennae. These results suggest that Rap/Fzr plays an essential role in the timely exit of precursor cells from mitotic cycles and indicate that mechanisms that regulate cell cycle exit are critical during pattern formation and morphogenesis.
rap（视网膜模式异常）基因编码Fizzy相关蛋白（Fzr），它作为泛素连接酶复合物的激活剂；后期促进复合物/细胞周期体（APC/C）促进细胞周期阶段特异性的细胞周期蛋白降解。rap基因的功能丧失突变导致发育中的眼成虫盘细胞周期蛋白B的异常积累，导致额外的有丝分裂周期以及发育中的果蝇眼睛模式缺陷。在眼原基细胞中靶向错误表达rap/fzr会导致过早的细胞周期退出，以及较小的原基眼场，这会消除或大幅减小成虫眼睛的大小。尽管在错误表达的动物中有丝分裂受到抑制，但细胞核异常大的细胞通过持续的核内复制、细胞生长和视网膜分化形成肿瘤样结构。有趣的是，在眼原基中过表达Rap/Fzr也会增加触角原基的大小，从而导致异位触角的诱导。这些结果表明，Rap/Fzr在前期细胞及时退出有丝分裂周期中起重要作用，并表明调节细胞周期退出的机制在模式形成和形态发生过程中至关重要。
