An Evolutionarily Conserved Enhancer Regulates Bmp4 Expression in Developing Incisor and Limb Bud

DSpace/Manakin Repository

An Evolutionarily Conserved Enhancer Regulates Bmp4 Expression in Developing Incisor and Limb Bud

Citable link to this page

 

 
Title: An Evolutionarily Conserved Enhancer Regulates Bmp4 Expression in Developing Incisor and Limb Bud
Author: Lachke, Salil A.; O’Connell, Daniel J.; Aboukhalil, Anton; Choe, Sung E.; Turbe-Doan, Annick; Robertson, Erin A.; Amendt, Brad A.; Jumlongras, Dolrudee; Li, Xiao; Ho, Joshua Wing Kei; Olsen, Bjorn Reino; Bulyk, Martha Leonia; Maas, Richard Louis

Note: Order does not necessarily reflect citation order of authors.

Citation: Jumlongras, Dolrudee, Salil A. Lachke, Daniel J. O’Connell, Anton Aboukhalil, Xiao Li, Sung E. Choe, Joshua W. K. Ho, et al. 2012. An evolutionarily conserved enhancer regulates Bmp4 expression in developing incisor and limb bud. PLoS ONE 7(6): e38568.
Full Text & Related Files:
Abstract: To elucidate the transcriptional regulation of Bmp4 expression during organogenesis, we used phylogenetic footprinting and transgenic reporter analyses to identify Bmp4 cis-regulatory modules (CRMs). These analyses identified a regulatory region located \(\sim\)46 kb upstream of the mouse Bmp4 transcription start site that had previously been shown to direct expression in lateral plate mesoderm. We refined this regulatory region to a 396-bp minimal enhancer, and show that it recapitulates features of endogenous Bmp4 expression in developing mandibular arch ectoderm and incisor epithelium during the initiation-stage of tooth development. In addition, this enhancer directs expression in the apical ectodermal ridge (AER) of the developing limb and in anterior and posterior limb mesenchyme. Transcript profiling of E11.5 mouse incisor dental lamina, together with protein binding microarray (PBM) analyses, allowed identification of a conserved DNA binding motif in the Bmp4 enhancer for Pitx homeoproteins, which are also expressed in the developing mandibular and incisor epithelium. In vitro electrophoretic mobility shift assays (EMSA) and in vivo transgenic reporter mutational analyses revealed that this site supports Pitx binding and that the site is necessary to recapitulate aspects of endogenous Bmp4 expression in developing craniofacial and limb tissues. Finally, Pitx2 chromatin immunoprecipitation (ChIP) demonstrated direct binding of Pitx2 to this Bmp4 enhancer site in a dental epithelial cell line. These results establish a direct molecular regulatory link between Pitx family members and Bmp4 gene expression in developing incisor epithelium.
Published Version: doi:10.1371/journal.pone.0038568
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3373496/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10419470
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters