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Sci Rep January 1, 2017; 7 (1): 13004.
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SHH signaling directed by two oral epithelium-specific enhancers controls tooth and oral development.

Sagai T , Amano T , Maeno A , Kiyonari H , Seo H , Cho SW , Shiroishi T .

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.

PubMed ID: 29021530
PMC ID: PMC5636896
Article link: Sci Rep

Species referenced: Xenopus
Genes referenced: lef1 mmut shh tcf3

Article Images: [+] show captions
References [+] :
Ahn, Inhibition of Wnt signaling by Wise (Sostdc1) and negative feedback from Shh controls tooth number and patterning. 2010, Pubmed