Ma Lin, Hocking Jennifer C, Hehr Carrie L, Schuurmans Carol, McFarlane Sarah
Genes and Development Research Group, HBI, IMCH, 2207 HSC, University of Calgary, Calgary, AB, Canada.
Dev Dyn. 2007 Jan;236(1):192-202. doi: 10.1002/dvdy.21002.
The timing of cell cycle exit is tightly linked to cell fate specification in the developing retina. Accordingly, several tumor suppressor genes, which are key regulators of cell cycle exit in cancer cells, play critical roles in retinogenesis. Here we investigated the role of Zac1, a tumor suppressor gene encoding a zinc finger transcription factor, in retinal development. Strikingly, in gain-of-function assays in Xenopus, mouse Zac1 promotes proliferation and apoptosis at an intermediate stage of retinogenesis. Zac1 also influences cell fate decisions, preferentially promoting the differentiation of tumor-like clusters of abnormal neuronal cells in the ganglion cell layer, as well as inducing the formation of supernumerary Müller glial cells at the expense of other cell types. Thus Zac1 has the capacity to influence cell cycle exit, and cell fate specification and differentiation decisions by retinal progenitors, suggesting that further functional studies will uncover new insights into how retinogenesis is regulated.
细胞周期退出的时间与发育中的视网膜中的细胞命运决定紧密相关。因此,几个肿瘤抑制基因,它们是癌细胞中细胞周期退出的关键调节因子,在视网膜发生过程中发挥着关键作用。在这里,我们研究了Zac1,一个编码锌指转录因子的肿瘤抑制基因,在视网膜发育中的作用。令人惊讶的是,在非洲爪蟾和小鼠的功能获得实验中,Zac1在视网膜发生的中间阶段促进增殖和凋亡。Zac1还影响细胞命运决定,优先促进神经节细胞层中异常神经元细胞的肿瘤样簇的分化,并以牺牲其他细胞类型为代价诱导额外的米勒胶质细胞的形成。因此,Zac1有能力影响细胞周期退出以及视网膜祖细胞的细胞命运决定和分化决定,这表明进一步的功能研究将揭示视网膜发生如何被调控的新见解。