Upstream Enhancer Elements of Shh Regulate Oral and Dental Patterning

Journal of Dental Research
Hyejin SeoToshihiko Shiroishi

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.

References

Dec 19, 2000·Mechanisms of Development·P KrausC A Loomis
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Laura A LetticeSumihare Noji
Nov 19, 2003·Developmental Biology·Kinga MichnoPaul A Hamel
Jan 17, 2004·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Tomoko SagaiToshihiko Shiroishi
Sep 20, 2005·Developmental Biology·Changgong LiParviz Minoo
Sep 24, 2005·Science·Yoshiaki KassaiNobuyuki Itoh
Feb 8, 2006·Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution·Renata PeterkovaMiroslav Peterka
Nov 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Elina JärvinenIrma Thesleff
Feb 8, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ken IwatsukiRobert F Margolskee
Nov 21, 2007·Developmental Biology·Fei LiuSarah E Millar
Aug 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jan ProchazkaRenata Peterkova
Nov 1, 2011·Histochemistry and Cell Biology·Jong-Min LeeHan-Sung Jung

❮ Previous
Next ❯

Citations

Oct 17, 2018·Journal of Dental Research·J KimS W Cho
Mar 1, 2020·International Journal of Molecular Sciences·Akihiro HosoyaKazuharu Irie
Apr 29, 2020·Development, Growth & Differentiation·Takanori Amano
Sep 10, 2019·Journal of Dental Research·J LiZ Zhang
Nov 20, 2021·Journal of Dental Research·M SeppalaM T Cobourne

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
immunoprecipitation

Software Mentioned

ECR Browser
UCSC genome browser

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.