spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 15 April 2009
doi: 10.1242/dev.032714

Development 136, 1665-1674 (2009)
Published by The Company of Biologists 2009
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
dev.032714v1
136/10/1665    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in Development
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Google Scholar
Right arrow Articles by Sagai, T.
Right arrow Articles by Shiroishi, T.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sagai, T.
Right arrow Articles by Shiroishi, T.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

A cluster of three long-range enhancers directs regional Shh expression in the epithelial linings

Tomoko Sagai1, Takanori Amano1, Masaru Tamura1, Yoichi Mizushina1, Kenta Sumiyama2 and Toshihiko Shiroishi1,*

1 Mammalian Genetics Laboratory, National Institute of Genetics, Yata-1111 Mishima Shizuoka-ken 411-8540, Japan.
2 Population Genetics Laboratory, National Institute of Genetics, Yata-1111 Mishima Shizuoka-ken 411-8540, Japan.

* Author for correspondence (e-mail: tshirois{at}lab.nig.ac.jp)

Accepted 10 March 2009

The sonic hedgehog (Shh) pathway plays indispensable roles in the morphogenesis of mouse epithelial linings of the oral cavity and respiratory and digestive tubes. However, no enhancers that regulate regional Shh expression within the epithelial linings have been identified so far. In this study, comparison of genomic sequences across mammalian species and teleost fishes revealed three novel conserved non-coding sequences (CNCSs) that cluster in a region 600 to 900 kb upstream of the transcriptional start site of the mouse Shh gene. These CNCSs drive regional transgenic lacZ reporter expression in the epithelial lining of the oral cavity, pharynx, lung and gut. Together, these enhancers recapitulate the endogenous Shh expression domain within the major epithelial linings. Notably, genomic arrangement of the three CNCSs shows co-linearity that mirrors the order of the epithelial expression domains along the anteroposterior body axis. The results suggest that the three CNCSs are epithelial lining-specific long-range Shh enhancers, and that their actions partition the continuous epithelial linings into three domains: ectoderm-derived oral cavity, endoderm-derived pharynx, and respiratory and digestive tubes of the mouse. Targeted deletion of the pharyngeal epithelium specific CNCS results in loss of endogenous Shh expression in the pharynx and postnatal lethality owing to hypoplasia of the soft palate, epiglottis and arytenoid. Thus, this long-range enhancer is indispensable for morphogenesis of the pharyngeal apparatus.

Key words: Sonic hedgehog, Conserved non-coding sequence, Long-range enhancer, Epithelial lining, Mouse


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related articles in Development:

Sonic hedgehog enhanced from a distance

Development 2009 136: e1004. [Full Text]  



This article has been cited by other articles:


Home page
 Brief Funct Genomic ProteomicHome page
P. Navratilova and T. S. Becker
Genomic regulatory blocks in vertebrates and implications in human disease
Brief Funct Genomic Proteomic, July 1, 2009; 8(4): 333 - 342.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2009