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Upstream Enhancer Elements of Shh Regulate Oral and Dental Patterning

Authors
 H. Seo  ;  T. Amano  ;  R. Seki  ;  T. Sagai  ;  J. Kim  ;  S.W. Cho  ;  T. Shiroishi 
Citation
 JOURNAL OF DENTAL RESEARCH, Vol.97(9) : 1055-1063, 2018 
Journal Title
 JOURNAL OF DENTAL RESEARCH 
ISSN
 0022-0345 
Issue Date
2018
Keywords
Shh protein ; Wnt signaling pathway ; conserved sequence ; embryonic development ; sequence deletion ; tooth germ
Abstract
Sonic hedgehog ( Shh) is important in pattern formation during development. Shh transcription is modulated by a long-range regulatory mechanism containing a number of enhancers, which are spread over nearly 850 kb in the mouse genome. Shh enhancers in the nervous system have been found between intron and 430 kb upstream of Shh. Enhancers in the oral cavity, pharynx, lung, gut, and limbs have been discovered between 610 kb and 850 kb upstream of Shh. However, the intergenic region ranging from 430 to 610 kb upstream of Shh remains to be elucidated. In the present study, we found a novel long-range enhancer located 558 kb upstream of Shh. The enhancer showed in vivo activity in oral cavity and whiskers. A targeted deletion from the novel enhancer to mammal reptile conserved sequence 1 (MRCS1), which is a known enhancer of Shh in oral cavity, resulted in supernumerary molar formation, confirming the essential role of this intergenic region for Shh transcription in teeth. Furthermore, we clarified the binding of Lef1/Tcfs to the new enhancer and MRCS1, suggesting that Wnt/β-catenin signaling regulates Shh signaling in the oral cavity via these enhancers.
Full Text
http://journals.sagepub.com/doi/abs/10.1177/0022034518758642
DOI
10.1177/0022034518758642
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jin Sun(김진선) ORCID logo https://orcid.org/0000-0002-5089-3711
Cho, Sung Won(조성원) ORCID logo https://orcid.org/0000-0001-7505-9769
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/163197
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