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Science  16 Sep 2005:
Vol. 309, Issue 5742, pp. 1791
DOI: 10.1126/science.309.5742.1791c

Control of cell differentiation is thought to result from bistable regulatory networks that allow a transient developmental signal to instruct cells to adopt a differentiated state. In the nematode Caenorhabditis elegans, Johnston et al. examined a network that determines the alternative fates of two taste receptor neurons, known as ASE left (ASEL) and ASE right (ASER). These neurons are bilaterally symmetric but express distinct sets of chemoreceptors that are necessary for the worm's navigation in search of food. The authors find through genetic analysis that two key transcription factors, DIE-1 and COG-1, which promote the expression of genes specific to ASEL and ASER neurons, respectively, act in a feedback loop in which they are linked by two microRNAs (miRNAs) encoded by lsy-6 and mir-273. Expression of lsy-6 is enhanced by DIE-1, and the lsy-6 miRNA inhibits the expression of ASER-promoting factor COG-1, which in turn promotes the expression of mir-273 miRNA, which closes the loop by inhibiting expression of the ASEL-inducing gene die-1. Although the stimulus that causes switching of this loop to favor production of one or the other transcription factor remains unknown, the results provide the essence of a miRNA-containing transcriptional feedback loop that can account for the stabilized expression of terminal cell fate in the ASER and ASEL neurons. — LBR

Proc. Natl. Acad. Sci. U.S.A. 102, 12449 (2005).

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