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PLoS Biol 2006 Sep 01;49:e272. doi: 10.1371/journal.pbio.0040272.
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Timing the generation of distinct retinal cells by homeobox proteins.

Decembrini S , Andreazzoli M , Vignali R , Barsacchi G , Cremisi F .

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.

PubMed ID: 16903786
PMC ID: PMC1540709
Article link: PLoS Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: clock crx e2f3 e2f6 elavl1 otx2 prox1 rbp3 rbpms2 th tubb2b vsx1
Antibodies: Crx Ab1 Muller Glia Ab1 Otx2 Ab1 Vsx1 Ab1

Article Images: [+] show captions
References [+] :
Alexiades, Quantitative analysis of proliferation and cell cycle length during development of the rat retina. 1996, Pubmed