A novel enhancer of Shh in tooth development

Abstract

Sonic hedgehog (Shh) is a highly regulated gene that plays a major role in pattern formation in the devel opmental process. The Regulation of Shh is dependent on a long-range regulatory mechanism consisting of multiple enhancers which are scattered over nearly 850 kb in the mouse genome. Nervous system enhancers have been uncovered between intron and 430 kb upstream of Shh. The intergenic region from 430 kb to 850 kb has been reported to be a residence for enhancers in the oral cavity, pharynx, lungs, gut, and limbs. However, the intergenic region from 430 kb to 550 kb upstream of Shh have not been studied in detail. In this study, we found a novel long-range enhancer located 502 kb upstream of Shh in mouse. The en hancer named MRCS2 showed a physical interaction with the Shh promoter in the developing tooth. The pattern of MRCS2 activation did not match the pattern of Shh expression, indicating that MRCS2 does not de termine the localization of Shh expression. Phenotypic change was not observed in the MRCS2-deleted mice, indicating that deletion of MRCS2 alone could not cause morphological changes in teeth. These results suggest that although MRCS2 regulates the expression level of Shh, the deficiency of MRCS2 is sufficiently compen sated by other enhancers