The canonical Wnt signaling antagonist DKK2 is an essential effector of PITX2 function during normal eye development
Identifieur interne : 002766 ( Pmc/Corpus ); précédent : 002765; suivant : 002767The canonical Wnt signaling antagonist DKK2 is an essential effector of PITX2 function during normal eye development
Auteurs : Philip J. Gage ; Min Qian ; Dianqing Wu ; Kevin I. RosenbergSource :
- Developmental biology [ 0012-1606 ] ; 2008.
Abstract
Local control of cell signaling activity and integration of inputs from multiple signaling pathways are central for normal development but the underlying mechanisms remain poorly understood. Here we show that
Url:
DOI: 10.1016/j.ydbio.2008.02.030
PubMed: 18367164
PubMed Central: 2387126
Links to Exploration step
PMC:2387126Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The canonical Wnt signaling antagonist DKK2 is an essential effector of PITX2 function during normal eye development</title>
<author><name sortKey="Gage, Philip J" sort="Gage, Philip J" uniqKey="Gage P" first="Philip J." last="Gage">Philip J. Gage</name>
<affiliation><nlm:aff id="A1"> Department of Ophthalmology & Visual Sciences, University of Michigan Medical School, Ann Arbor, MI 48105</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2"> Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48105</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Qian, Min" sort="Qian, Min" uniqKey="Qian M" first="Min" last="Qian">Min Qian</name>
<affiliation><nlm:aff id="A1"> Department of Ophthalmology & Visual Sciences, University of Michigan Medical School, Ann Arbor, MI 48105</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wu, Dianqing" sort="Wu, Dianqing" uniqKey="Wu D" first="Dianqing" last="Wu">Dianqing Wu</name>
<affiliation><nlm:aff id="A3"> Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rosenberg, Kevin I" sort="Rosenberg, Kevin I" uniqKey="Rosenberg K" first="Kevin I." last="Rosenberg">Kevin I. Rosenberg</name>
<affiliation><nlm:aff id="A1"> Department of Ophthalmology & Visual Sciences, University of Michigan Medical School, Ann Arbor, MI 48105</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">18367164</idno>
<idno type="pmc">2387126</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2387126</idno>
<idno type="RBID">PMC:2387126</idno>
<idno type="doi">10.1016/j.ydbio.2008.02.030</idno>
<date when="2008">2008</date>
<idno type="wicri:Area/Pmc/Corpus">002766</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002766</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">The canonical Wnt signaling antagonist DKK2 is an essential effector of PITX2 function during normal eye development</title>
<author><name sortKey="Gage, Philip J" sort="Gage, Philip J" uniqKey="Gage P" first="Philip J." last="Gage">Philip J. Gage</name>
<affiliation><nlm:aff id="A1"> Department of Ophthalmology & Visual Sciences, University of Michigan Medical School, Ann Arbor, MI 48105</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2"> Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48105</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Qian, Min" sort="Qian, Min" uniqKey="Qian M" first="Min" last="Qian">Min Qian</name>
<affiliation><nlm:aff id="A1"> Department of Ophthalmology & Visual Sciences, University of Michigan Medical School, Ann Arbor, MI 48105</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wu, Dianqing" sort="Wu, Dianqing" uniqKey="Wu D" first="Dianqing" last="Wu">Dianqing Wu</name>
<affiliation><nlm:aff id="A3"> Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rosenberg, Kevin I" sort="Rosenberg, Kevin I" uniqKey="Rosenberg K" first="Kevin I." last="Rosenberg">Kevin I. Rosenberg</name>
<affiliation><nlm:aff id="A1"> Department of Ophthalmology & Visual Sciences, University of Michigan Medical School, Ann Arbor, MI 48105</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Developmental biology</title>
<idno type="ISSN">0012-1606</idno>
<idno type="eISSN">1095-564X</idno>
<imprint><date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Summary</title>
<p id="P3">Local control of cell signaling activity and integration of inputs from multiple signaling pathways are central for normal development but the underlying mechanisms remain poorly understood. Here we show that <italic>Dkk2</italic>
, encoding an antagonist of canonical Wnt signaling, is an essential downstream target of the PITX2 homeodomain transcription factor in neural crest during eye development. Canonical Wnt signaling is ectopically activated in central ocular surface ectoderm and underlying mesenchyme in <italic>Pitx2</italic>
and <italic>Dkk2</italic>
deficient mice. General ocular surface ectoderm identity is maintained during development in <italic>Dkk2</italic>
deficient mice but peripheral fates, including conjunctival goblet cells and eyelash follicles, are ectopically permitted within more central structures and eyelids are hypomorphic. Loss of DKK2 results in ectopic blood vessels within the periocular mesenchyme and PITX2 expression remains persistently high, providing evidence for a negative feedback loop. Collectively, these data suggest that activation of <italic>Dkk2</italic>
by PITX2 provides a mechanism to locally suppress canonical Wnt signaling activity during eye development, a paradigm that may be a model for achieving local or transient inhibition of pathway activity elsewhere during embryogenesis. We further propose a model placing PITX2 as an essential integration node between retinoic acid and canonical Wnt signaling during eye development.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0372762</journal-id>
<journal-id journal-id-type="pubmed-jr-id">3389</journal-id>
<journal-id journal-id-type="nlm-ta">Dev Biol</journal-id>
<journal-title>Developmental biology</journal-title>
<issn pub-type="ppub">0012-1606</issn>
<issn pub-type="epub">1095-564X</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">18367164</article-id>
<article-id pub-id-type="pmc">2387126</article-id>
<article-id pub-id-type="doi">10.1016/j.ydbio.2008.02.030</article-id>
<article-id pub-id-type="manuscript">NIHMS49872</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>The canonical Wnt signaling antagonist DKK2 is an essential effector of PITX2 function during normal eye development</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Gage</surname>
<given-names>Philip J.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A2" ref-type="aff">2</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Qian</surname>
<given-names>Min</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wu</surname>
<given-names>Dianqing</given-names>
</name>
<xref rid="A3" ref-type="aff">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rosenberg</surname>
<given-names>Kevin I.</given-names>
</name>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Ophthalmology & Visual Sciences, University of Michigan Medical School, Ann Arbor, MI 48105</aff>
<aff id="A2"><label>2</label>
Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48105</aff>
<aff id="A3"><label>3</label>
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520</aff>
<author-notes><corresp id="FN1"><label>*</label>
Corresponding author: Philip J. Gage, Department of Ophthalmology & Visual Sciences, University of Michigan Medical School, 350 Kellogg Eye Center, 1000 Wall Street, Ann Arbor, MI 48105, 734.647.4215 (Telephone), 734.936.7231 (FAX), <email>philgage@umich.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>7</day>
<month>5</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="epub"><day>4</day>
<month>3</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="ppub"><day>1</day>
<month>5</month>
<year>2008</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>5</month>
<year>2009</year>
</pub-date>
<volume>317</volume>
<issue>1</issue>
<fpage>310</fpage>
<lpage>324</lpage>
<abstract><title>Summary</title>
<p id="P3">Local control of cell signaling activity and integration of inputs from multiple signaling pathways are central for normal development but the underlying mechanisms remain poorly understood. Here we show that <italic>Dkk2</italic>
, encoding an antagonist of canonical Wnt signaling, is an essential downstream target of the PITX2 homeodomain transcription factor in neural crest during eye development. Canonical Wnt signaling is ectopically activated in central ocular surface ectoderm and underlying mesenchyme in <italic>Pitx2</italic>
and <italic>Dkk2</italic>
deficient mice. General ocular surface ectoderm identity is maintained during development in <italic>Dkk2</italic>
deficient mice but peripheral fates, including conjunctival goblet cells and eyelash follicles, are ectopically permitted within more central structures and eyelids are hypomorphic. Loss of DKK2 results in ectopic blood vessels within the periocular mesenchyme and PITX2 expression remains persistently high, providing evidence for a negative feedback loop. Collectively, these data suggest that activation of <italic>Dkk2</italic>
by PITX2 provides a mechanism to locally suppress canonical Wnt signaling activity during eye development, a paradigm that may be a model for achieving local or transient inhibition of pathway activity elsewhere during embryogenesis. We further propose a model placing PITX2 as an essential integration node between retinoic acid and canonical Wnt signaling during eye development.</p>
</abstract>
<kwd-group><kwd>homeobox</kwd>
<kwd>canonical Wnt signaling</kwd>
<kwd>mouse</kwd>
</kwd-group>
<contract-num rid="EY1">R01 EY014126-05</contract-num>
<contract-num rid="EY1">R01 EY014126-04A1</contract-num>
<contract-num rid="EY1">R01 EY014126-03</contract-num>
<contract-sponsor id="EY1">National Eye Institute : NEI</contract-sponsor>
</article-meta>
</front>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002766 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 002766 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= LymphedemaV1 |flux= Pmc |étape= Corpus |type= RBID |clé= PMC:2387126 |texte= The canonical Wnt signaling antagonist DKK2 is an essential effector of PITX2 function during normal eye development }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:18367164" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \ | NlmPubMed2Wicri -a LymphedemaV1
![]() | This area was generated with Dilib version V0.6.31. | ![]() |