Format

Send to

Choose Destination
Sci Rep. 2017 Oct 11;7(1):13004. doi: 10.1038/s41598-017-12532-y.

SHH signaling directed by two oral epithelium-specific enhancers controls tooth and oral development.

Author information

1
Mammalian Genetics Laboratory, National Institute of Genetics, Mishima, Shizuoka, Japan.
2
Animal Resource Development Unit and Genetic Engineering Team, RIKEN Center for Life Science Technologies, Kobe, Hyogo, 650-0047, Japan.
3
Division of Anatomy and Developmental Biology, Department of Oral Biology, Yonsei University College of Dentistry, Seoul, Korea.
4
Mammalian Genetics Laboratory, National Institute of Genetics, Mishima, Shizuoka, Japan. tshirois@nig.ac.jp.

Abstract

Interaction between the epithelium and mesenchyme coordinates patterning and differentiation of oral cavity structures including teeth, palatal rugae and tongue papillae. SHH is one of the key signaling molecules for this interaction. Epithelial expression of Shh in the tooth buds and tongue papillae is regulated by at least two enhancers, MRCS1 and MFCS4. However, it is unclear how the two enhancers cooperate to regulate Shh. Here, we found that simultaneous deletion of MRCS1 and MFCS4 results in the formation of a supernumerary tooth in front of the first molar. Since deletion of either single enhancer barely affects tooth development, MRCS1 and MFCS4 evidently act in a redundant fashion. Binding motifs for WNT signaling mediators are shared by MRCS1 and MFCS4, and play a central role in regulating Shh expression, indicating that the two redundant enhancers additively exert their Shh regulation by responding to WNT signal input.

PMID:
29021530
PMCID:
PMC5636896
DOI:
10.1038/s41598-017-12532-y
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center