Fly Fishing with a Hedgehog

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Science  23 Jan 2009:
Vol. 323, Issue 5913, pp. 439
DOI: 10.1126/science.323.5913.439c

The complexity of gene regulation mechanisms is also evident in the analysis by Amano et al. of the temporal and spatial patterns of Sonic hedgehog (Shh) expression. Shh is required for proper limb formation in mice. In the limb bud, it is expressed exclusively in a group of posterior mesenchymal cells called the zone of polarizing activity (ZPA). The authors found that colocalization of the Shh coding region and the long-range enhancer of its expression in limb bud, MFCS1, frequently occurs in the ZPA of day-10.5 limb buds but not by day 12.5, when Shh has been turned off. Chromosome conformation capture assays confirmed that MFCS1 and Shh interact directly in the limb bud. This interaction appears to indicate transcriptional competence; for active transcription to occur, a chromosome loop involving Shh needs to form, and evidence of loop formation was seen only in the ZPA. Such loops have been observed in other systems, and the authors propose that the interaction of MFCS1 and Shh promotes a looping-out of the chromosome that renders Shh accessible to transcription factors. This change in chromosomal configuration was observed in only a fraction of the ZPA cells at any one time; the resultant intermittent exposure of Shh may ensure proper control of levels of Shh needed for limb morphogenesis. — BJ

Dev. Cell 16, 10.1016/j.devcel.2008.11.011 (2009).

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