FGF-regulated BMP signaling is required for eyelid closure and to specify conjunctival epithelial cell fate
Identifieur interne : 006288 ( Main/Exploration ); précédent : 006287; suivant : 006289FGF-regulated BMP signaling is required for eyelid closure and to specify conjunctival epithelial cell fate
Auteurs : Jie Huang [États-Unis] ; Lisa K. Dattilo [États-Unis] ; Ramya Rajagopal [États-Unis] ; Ying Liu [États-Unis] ; Vesa Kaartinen [États-Unis] ; Yuji Mishina [États-Unis] ; Chu-Xia Deng [États-Unis] ; Lieve Umans [Belgique] ; An Zwijsen [Belgique] ; Anita B. Roberts [États-Unis] ; David C. Beebe [États-Unis]Source :
- Development (Cambridge, England) [ 0950-1991 ] ; 2009.
Descripteurs français
- KwdFr :
- Animaux, Animaux nouveau-nés, Cellules épithéliales (cytologie), Cellules épithéliales (métabolisme), Conjonctive (croissance et développement), Conjonctive (cytologie), Conjonctive (embryologie), Conjonctive (malformations), Différenciation cellulaire (physiologie), Facteurs de croissance fibroblastique (physiologie), Facteurs de transcription Forkhead (métabolisme), Follicule pileux (croissance et développement), Follicule pileux (embryologie), JNK Mitogen-Activated Protein Kinases (métabolisme), Paupières (croissance et développement), Paupières (embryologie), Paupières (malformations), Protéine Smad-4 (génétique), Protéine Smad-4 (métabolisme), Protéine morphogénétique osseuse de type 4 (biosynthèse), Protéines Hedgehog (métabolisme), Protéines Smad régulées par les récepteurs (génétique), Protéines morphogénétiques osseuses (physiologie), Récepteur FGFR2 (génétique), Récepteur FGFR2 (métabolisme), Récepteurs de la protéine morphogénique osseuse de type I (génétique), Souris, Souris knockout, Transduction du signal.
- MESH :
- biosynthèse : Protéine morphogénétique osseuse de type 4.
- croissance et développement : Conjonctive, Follicule pileux, Paupières.
- cytologie : Cellules épithéliales, Conjonctive.
- embryologie : Conjonctive, Follicule pileux, Paupières.
- génétique : Protéine Smad-4, Protéines Smad régulées par les récepteurs, Récepteur FGFR2, Récepteurs de la protéine morphogénique osseuse de type I.
- malformations : Conjonctive, Paupières.
- métabolisme : Cellules épithéliales, Facteurs de transcription Forkhead, JNK Mitogen-Activated Protein Kinases, Protéine Smad-4, Protéines Hedgehog, Récepteur FGFR2.
- physiologie : Différenciation cellulaire, Facteurs de croissance fibroblastique, Protéines morphogénétiques osseuses.
- Animaux, Animaux nouveau-nés, Souris, Souris knockout, Transduction du signal.
English descriptors
- KwdEn :
- Animals, Animals, Newborn, Bone Morphogenetic Protein 4 (biosynthesis), Bone Morphogenetic Protein Receptors, Type I (genetics), Bone Morphogenetic Proteins (physiology), Cell Differentiation (physiology), Conjunctiva (abnormalities), Conjunctiva (cytology), Conjunctiva (embryology), Conjunctiva (growth & development), Epithelial Cells (cytology), Epithelial Cells (metabolism), Eyelids (abnormalities), Eyelids (embryology), Eyelids (growth & development), Fibroblast Growth Factors (physiology), Forkhead Transcription Factors (metabolism), Hair Follicle (embryology), Hair Follicle (growth & development), Hedgehog Proteins (metabolism), JNK Mitogen-Activated Protein Kinases (metabolism), Mice, Mice, Knockout, Receptor, Fibroblast Growth Factor, Type 2 (genetics), Receptor, Fibroblast Growth Factor, Type 2 (metabolism), Signal Transduction, Smad Proteins, Receptor-Regulated (genetics), Smad4 Protein (genetics), Smad4 Protein (metabolism).
- MESH :
- chemical , biosynthesis : Bone Morphogenetic Protein 4.
- chemical , genetics : Bone Morphogenetic Protein Receptors, Type I, Receptor, Fibroblast Growth Factor, Type 2, Smad Proteins, Receptor-Regulated, Smad4 Protein.
- chemical , metabolism : Forkhead Transcription Factors, Hedgehog Proteins, JNK Mitogen-Activated Protein Kinases, Receptor, Fibroblast Growth Factor, Type 2, Smad4 Protein.
- chemical , physiology : Bone Morphogenetic Proteins, Fibroblast Growth Factors.
- abnormalities : Conjunctiva, Eyelids.
- cytology : Conjunctiva, Epithelial Cells.
- embryology : Conjunctiva, Eyelids, Hair Follicle.
- growth & development : Conjunctiva, Eyelids, Hair Follicle.
- metabolism : Epithelial Cells.
- physiology : Cell Differentiation.
- Animals, Animals, Newborn, Mice, Mice, Knockout, Signal Transduction.
Abstract
There are conflicting reports about whether BMP signaling is required for
eyelid closure during fetal development. This question was addressed using
mice deficient in BMP or TGFβ signaling in prospective eyelid and
conjunctival epithelial cells. Genes encoding two type I BMP receptors, the
type II TGFβ receptor, two BMP- or two TGFβ-activated R-Smads or the
co-Smad Smad4 were deleted from the ocular surface ectoderm using Cre
recombinase. Only mice with deletion of components of the BMP pathway had an
`eyelid open at birth' phenotype. Mice lacking
Url:
DOI: 10.1242/dev.034082
PubMed: 19369394
PubMed Central: 2673764
Affiliations:
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Le document en format XML
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<author><name sortKey="Mishina, Yuji" sort="Mishina, Yuji" uniqKey="Mishina Y" first="Yuji" last="Mishina">Yuji Mishina</name>
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<author><name sortKey="Deng, Chu Xia" sort="Deng, Chu Xia" uniqKey="Deng C" first="Chu-Xia" last="Deng">Chu-Xia Deng</name>
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<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
<wicri:regionArea> Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892</wicri:regionArea>
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<country xml:lang="fr" wicri:curation="lc">États-Unis</country>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Animals, Newborn</term>
<term>Bone Morphogenetic Protein 4 (biosynthesis)</term>
<term>Bone Morphogenetic Protein Receptors, Type I (genetics)</term>
<term>Bone Morphogenetic Proteins (physiology)</term>
<term>Cell Differentiation (physiology)</term>
<term>Conjunctiva (abnormalities)</term>
<term>Conjunctiva (cytology)</term>
<term>Conjunctiva (embryology)</term>
<term>Conjunctiva (growth & development)</term>
<term>Epithelial Cells (cytology)</term>
<term>Epithelial Cells (metabolism)</term>
<term>Eyelids (abnormalities)</term>
<term>Eyelids (embryology)</term>
<term>Eyelids (growth & development)</term>
<term>Fibroblast Growth Factors (physiology)</term>
<term>Forkhead Transcription Factors (metabolism)</term>
<term>Hair Follicle (embryology)</term>
<term>Hair Follicle (growth & development)</term>
<term>Hedgehog Proteins (metabolism)</term>
<term>JNK Mitogen-Activated Protein Kinases (metabolism)</term>
<term>Mice</term>
<term>Mice, Knockout</term>
<term>Receptor, Fibroblast Growth Factor, Type 2 (genetics)</term>
<term>Receptor, Fibroblast Growth Factor, Type 2 (metabolism)</term>
<term>Signal Transduction</term>
<term>Smad Proteins, Receptor-Regulated (genetics)</term>
<term>Smad4 Protein (genetics)</term>
<term>Smad4 Protein (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Animaux nouveau-nés</term>
<term>Cellules épithéliales (cytologie)</term>
<term>Cellules épithéliales (métabolisme)</term>
<term>Conjonctive (croissance et développement)</term>
<term>Conjonctive (cytologie)</term>
<term>Conjonctive (embryologie)</term>
<term>Conjonctive (malformations)</term>
<term>Différenciation cellulaire (physiologie)</term>
<term>Facteurs de croissance fibroblastique (physiologie)</term>
<term>Facteurs de transcription Forkhead (métabolisme)</term>
<term>Follicule pileux (croissance et développement)</term>
<term>Follicule pileux (embryologie)</term>
<term>JNK Mitogen-Activated Protein Kinases (métabolisme)</term>
<term>Paupières (croissance et développement)</term>
<term>Paupières (embryologie)</term>
<term>Paupières (malformations)</term>
<term>Protéine Smad-4 (génétique)</term>
<term>Protéine Smad-4 (métabolisme)</term>
<term>Protéine morphogénétique osseuse de type 4 (biosynthèse)</term>
<term>Protéines Hedgehog (métabolisme)</term>
<term>Protéines Smad régulées par les récepteurs (génétique)</term>
<term>Protéines morphogénétiques osseuses (physiologie)</term>
<term>Récepteur FGFR2 (génétique)</term>
<term>Récepteur FGFR2 (métabolisme)</term>
<term>Récepteurs de la protéine morphogénique osseuse de type I (génétique)</term>
<term>Souris</term>
<term>Souris knockout</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Bone Morphogenetic Protein 4</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Bone Morphogenetic Protein Receptors, Type I</term>
<term>Receptor, Fibroblast Growth Factor, Type 2</term>
<term>Smad Proteins, Receptor-Regulated</term>
<term>Smad4 Protein</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Forkhead Transcription Factors</term>
<term>Hedgehog Proteins</term>
<term>JNK Mitogen-Activated Protein Kinases</term>
<term>Receptor, Fibroblast Growth Factor, Type 2</term>
<term>Smad4 Protein</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Bone Morphogenetic Proteins</term>
<term>Fibroblast Growth Factors</term>
</keywords>
<keywords scheme="MESH" qualifier="abnormalities" xml:lang="en"><term>Conjunctiva</term>
<term>Eyelids</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Protéine morphogénétique osseuse de type 4</term>
</keywords>
<keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Conjonctive</term>
<term>Follicule pileux</term>
<term>Paupières</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Cellules épithéliales</term>
<term>Conjonctive</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Conjunctiva</term>
<term>Epithelial Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="embryologie" xml:lang="fr"><term>Conjonctive</term>
<term>Follicule pileux</term>
<term>Paupières</term>
</keywords>
<keywords scheme="MESH" qualifier="embryology" xml:lang="en"><term>Conjunctiva</term>
<term>Eyelids</term>
<term>Hair Follicle</term>
</keywords>
<keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Conjunctiva</term>
<term>Eyelids</term>
<term>Hair Follicle</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéine Smad-4</term>
<term>Protéines Smad régulées par les récepteurs</term>
<term>Récepteur FGFR2</term>
<term>Récepteurs de la protéine morphogénique osseuse de type I</term>
</keywords>
<keywords scheme="MESH" qualifier="malformations" xml:lang="fr"><term>Conjonctive</term>
<term>Paupières</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Epithelial Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules épithéliales</term>
<term>Facteurs de transcription Forkhead</term>
<term>JNK Mitogen-Activated Protein Kinases</term>
<term>Protéine Smad-4</term>
<term>Protéines Hedgehog</term>
<term>Récepteur FGFR2</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Différenciation cellulaire</term>
<term>Facteurs de croissance fibroblastique</term>
<term>Protéines morphogénétiques osseuses</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Cell Differentiation</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Animals, Newborn</term>
<term>Mice</term>
<term>Mice, Knockout</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Animaux nouveau-nés</term>
<term>Souris</term>
<term>Souris knockout</term>
<term>Transduction du signal</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Summary</title>
<p>There are conflicting reports about whether BMP signaling is required for
eyelid closure during fetal development. This question was addressed using
mice deficient in BMP or TGFβ signaling in prospective eyelid and
conjunctival epithelial cells. Genes encoding two type I BMP receptors, the
type II TGFβ receptor, two BMP- or two TGFβ-activated R-Smads or the
co-Smad Smad4 were deleted from the ocular surface ectoderm using Cre
recombinase. Only mice with deletion of components of the BMP pathway had an
`eyelid open at birth' phenotype. Mice lacking <italic>Fgf10</italic>
or
<italic>Fgfr2</italic>
also have open eyelids at birth. To better understand the
pathways that regulate BMP expression and function during eyelid development,
we localized BMPs and BMP signaling intermediates in <italic>Fgfr2</italic>
and
<italic>Smad4</italic>
conditional knockout (CKO) mice. We found that Fgfr2 was
required for the expression of <italic>Bmp4</italic>
, the normal distribution of Shh
signaling and for preserving the differentiation of the conjunctival
epithelium. FGF signaling also promoted the expression of the Wnt antagonist
Sfrp1 and suppressed Wnt signaling in the prospective eyelid epithelial cells,
independently of BMP function. Transcripts encoding Foxc1 and Foxc2, which
were previously shown to be necessary for eyelid closure, were not detectable
in <italic>Smad4<sup>CKO</sup>
</italic>
animals. c-Jun, another key regulator of
eyelid closure, was present and phosphorylated in eyelid periderm cells at the
time of fusion, but failed to translocate to the nucleus in the absence of BMP
function. <italic>Smad4<sup>CKO</sup>
</italic>
mice also showed premature
differentiation of the conjunctival epithelium, conjunctival hyperplasia and
the acquisition of epidermal characteristics, including formation of an
ectopic row of hair follicles in place of the Meibomian glands. A second row
of eyelashes is a feature of human lymphedema-distichiasis syndrome, which is
associated with mutations in FOXC2.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>Belgique</li>
<li>États-Unis</li>
</country>
<region><li>Californie</li>
</region>
<settlement><li>Los Angeles</li>
</settlement>
<orgName><li>Université de Californie du Sud</li>
</orgName>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Huang, Jie" sort="Huang, Jie" uniqKey="Huang J" first="Jie" last="Huang">Jie Huang</name>
</noRegion>
<name sortKey="Beebe, David C" sort="Beebe, David C" uniqKey="Beebe D" first="David C." last="Beebe">David C. Beebe</name>
<name sortKey="Beebe, David C" sort="Beebe, David C" uniqKey="Beebe D" first="David C." last="Beebe">David C. Beebe</name>
<name sortKey="Dattilo, Lisa K" sort="Dattilo, Lisa K" uniqKey="Dattilo L" first="Lisa K." last="Dattilo">Lisa K. Dattilo</name>
<name sortKey="Deng, Chu Xia" sort="Deng, Chu Xia" uniqKey="Deng C" first="Chu-Xia" last="Deng">Chu-Xia Deng</name>
<name sortKey="Kaartinen, Vesa" sort="Kaartinen, Vesa" uniqKey="Kaartinen V" first="Vesa" last="Kaartinen">Vesa Kaartinen</name>
<name sortKey="Liu, Ying" sort="Liu, Ying" uniqKey="Liu Y" first="Ying" last="Liu">Ying Liu</name>
<name sortKey="Mishina, Yuji" sort="Mishina, Yuji" uniqKey="Mishina Y" first="Yuji" last="Mishina">Yuji Mishina</name>
<name sortKey="Rajagopal, Ramya" sort="Rajagopal, Ramya" uniqKey="Rajagopal R" first="Ramya" last="Rajagopal">Ramya Rajagopal</name>
<name sortKey="Roberts, Anita B" sort="Roberts, Anita B" uniqKey="Roberts A" first="Anita B." last="Roberts">Anita B. Roberts</name>
</country>
<country name="Belgique"><noRegion><name sortKey="Umans, Lieve" sort="Umans, Lieve" uniqKey="Umans L" first="Lieve" last="Umans">Lieve Umans</name>
</noRegion>
<name sortKey="Umans, Lieve" sort="Umans, Lieve" uniqKey="Umans L" first="Lieve" last="Umans">Lieve Umans</name>
<name sortKey="Zwijsen, An" sort="Zwijsen, An" uniqKey="Zwijsen A" first="An" last="Zwijsen">An Zwijsen</name>
<name sortKey="Zwijsen, An" sort="Zwijsen, An" uniqKey="Zwijsen A" first="An" last="Zwijsen">An Zwijsen</name>
</country>
</tree>
</affiliations>
</record>
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