Timing the generation of distinct retinal cells by homeobox proteins.
Timing the generation of distinct retinal cells by homeobox proteins.
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DOI：
10.1371/journal.pbio.0040272
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发表时间：
2006-09
期刊：
影响因子：
9.8
通讯作者：
Cremisi F
中科院分区：
文献类型：
--
作者：
Decembrini S;Andreazzoli M;Vignali R;Barsacchi G;Cremisi F
为什么不同类型的脊椎动物神经细胞以特定的顺序产生，人们仍然知之甚少。在脊椎动物的视网膜中，同源盒基因在建立不同的细胞身份方面起着至关重要的作用。在这里，我们提供了细胞时钟的证据，它顺序地激活胚胎视网膜细胞中不同的同源框基因，将视网膜细胞的身份与其生成时间联系起来。通过原位表达分析，我们发现三个非洲爪哇同源框基因Xotx5b、Xvsx1和Xotx2最初在视网膜祖细胞中转录，但没有翻译。它们的翻译需要细胞周期的进展，在光感受器(Xotx5b)和双极细胞(Xvsx1和Xotx2)中依次激活。此外，通过体内脂质感染绿色荧光蛋白翻译受控于3‘非翻译区的“传感器”，我们发现Xotx5b、Xvsx1和Xotx2的3’非翻译区足以驱动与相应蛋白质匹配的时空翻译模式，并且与光感受器(Xotx5b)和双极细胞(Xvsx1和Xotx2)的产生时间一致。单个早期视网膜前体细胞的细胞周期进程受阻，阻碍了它们作为光感受器和双极细胞的分化，但分别通过Xotx5b和Xvsx1编码序列的脂质体感染而被挽救。这是我们所知的第一个证据，证明脊椎动物的同源框蛋白可以作为细胞时钟的效应器来建立不同的细胞身份。由同源异型盒基因的顺序翻译控制介导的细胞钟将非洲爪哇视网膜细胞的命运与它们的生成时间联系在一起。
The reason why different types of vertebrate nerve cells are generated in a particular sequence is still poorly understood. In the vertebrate retina, homeobox genes play a crucial role in establishing different cell identities. Here we provide evidence of a cellular clock that sequentially activates distinct homeobox genes in embryonic retinal cells, linking the identity of a retinal cell to its time of generation. By in situ expression analysis, we found that the three Xenopus homeobox genes Xotx5b, Xvsx1, and Xotx2 are initially transcribed but not translated in early retinal progenitors. Their translation requires cell cycle progression and is sequentially activated in photoreceptors (Xotx5b) and bipolar cells (Xvsx1 and Xotx2). Furthermore, by in vivo lipofection of “sensors” in which green fluorescent protein translation is under control of the 3′ untranslated region (UTR), we found that the 3′ UTRs of Xotx5b, Xvsx1, and Xotx2 are sufficient to drive a spatiotemporal pattern of translation matching that of the corresponding proteins and consistent with the time of generation of photoreceptors (Xotx5b) and bipolar cells (Xvsx1 and Xotx2). The block of cell cycle progression of single early retinal progenitors impairs their differentiation as photoreceptors and bipolar cells, but is rescued by the lipofection of Xotx5b and Xvsx1 coding sequences, respectively. This is the first evidence to our knowledge that vertebrate homeobox proteins can work as effectors of a cellular clock to establish distinct cell identities. A cellular clock mediated by sequential translational control of homeobox genes links retinal cell fates to their time of generation in Xenopus.