Linked Life Data

17397822

Source:http://linkedlifedata.com/resource/pubmed/id/17397822

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-5-7
pubmed:abstractText
Ectodermal appendage morphogenesis requires continuous epithelial-mesenchymal cross-talk during development. Canonical Wnt signaling has been shown to be pivotal during this process and its inhibition leads to the absence of any morphological or molecular signs of appendage formation, including hair follicles (HFs). In the mouse, primary HFs arise in utero starting just before E14.5, when the first morphological signs of a placode are discernible. In this study, our goal was to identify novel factors expressed during primary HF morphogenesis. We performed transcriptional profiling of the developing epidermis at 12 h intervals between E12.5 and E15.5. One of the significantly differentially expressed genes was the Wnt inhibitor Dickkopf 4, Dkk4. We show that Dkk4 mRNA increases sharply in the dorso-lateral epidermis around E14 and then decreases until E15.5. Using whole mount in situ hybridization, we show that Dkk4 mRNA is localized to the pre-placodes at sites of presumptive epithelial-mesenchymal interactions during appendage morphogenesis, including the dental lamina, mammary gland, eccrine gland, and primary and secondary HFs. In silico analysis, reporter gene assays as well as in vitro transfections of LEF1 and beta-catenin show that Dkk4 is a potential downstream target of canonical Wnt signaling. In addition, we demonstrate a direct physical interaction between LEF1/beta-catenin complex and the Dkk4 promoter using ChIP. We propose that Dkk4 acts in a negative feedback loop to attenuate canonical Wnt signaling, and may facilitate a switch to the non-canonical Wnt planar cell polarity (PCP) pathway that is involved in cell movements during morphogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0012-1606
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
305
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
498-507
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The Wnt inhibitor, Dickkopf 4, is induced by canonical Wnt signaling during ectodermal appendage morphogenesis.
pubmed:affiliation
Department of Genetics and Development, Columbia University, New York, NY, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Validation Studies