Different Roles of Runx2 During Early Neural Crest–Derived Bone and Tooth Development
We compared gene expression profiles between Runx2 null mutant mice and their wildtype littermates. Most Runx2‐dependent genes in bones were different from those in teeth, implying that the target genes of Runx2 are tissue‐dependent. In vitro experiments determined that Runx2 is a part of the FGF an...
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| Veröffentlicht in: | Journal of bone and mineral research 2006-07, Vol.21 (7), p.1034-1044 |
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| creator | James, Martyn J Järvinen, Elina Wang, Xiu‐Ping Thesleff, Irma |
| description | We compared gene expression profiles between Runx2 null mutant mice and their wildtype littermates. Most Runx2‐dependent genes in bones were different from those in teeth, implying that the target genes of Runx2 are tissue‐dependent. In vitro experiments determined that Runx2 is a part of the FGF and BMP signaling pathways in tooth and bone development, respectively.
Introduction: Runx2 (Cbfa1) is expressed in the neural crest–derived mesenchyme of developing bone and tooth. Runx2 homozygous null mice lack bone through a failure in osteoblast differentiation and have arrested tooth development at the late bud stage. The aim of this study was to discover and compare the identities and the roles of Runx2 target genes in bone and tooth development.
Materials and Methods: Wildtype and Runx2−/− tissue was collected from mouse embryos, and gene expression was compared by Affymetrix microarray analysis and radioactive in situ hybridization of embryonic tissue sections (E12–E14). Induction of target genes by growth factors in bone and tooth tissue was studied using in vitro experiments, including a novel method involving hanging‐drop cultures and RT‐PCR.
Results: Thirteen bone and four tooth genes were identified that are Runx2‐dependent. The identities of these genes do not significantly overlap between bone and tooth, indicating tissue specificity of several genes regulated by Runx2. Genes downregulated in bone development in Runx2 null mutants were Bambi, Bmp4, Bono1, Dkk1, Fgf receptor1, Gli1, Lef1, Patched, Prostaglandin F receptor1, Tcf1, Tgfβ1, Wnt10a, and Wnt10b. Several of these genes were induced by BMPs in bone tissue in a Runx2‐independent manner. Genes downregulated in tooth development were Dkk1, Dusp6, Enpp1, and Igfbp3. These genes were all induced by fibroblast growth factors (FGFs) in dental tissue. FGF‐induction of Dkk1 was completely dependent on Runx2 function.
Conclusions: The contrasting identities and distinctive mechanisms that stimulate the expression of Runx2‐dependent genes in bone and tooth development imply that the developmental roles of Runx2 in these separate tissues are different. In tooth development, Dkk1 may be a direct transcriptional target of Runx2. Bone genes were stimulated by BMP4 before the formation of the ossification center, suggesting that BMPs may mediate the early epithelial–mesenchymal interactions involved in bone formation. |
| doi_str_mv | 10.1359/jbmr.060413 |
| format | Article |
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Introduction: Runx2 (Cbfa1) is expressed in the neural crest–derived mesenchyme of developing bone and tooth. Runx2 homozygous null mice lack bone through a failure in osteoblast differentiation and have arrested tooth development at the late bud stage. The aim of this study was to discover and compare the identities and the roles of Runx2 target genes in bone and tooth development.
Materials and Methods: Wildtype and Runx2−/− tissue was collected from mouse embryos, and gene expression was compared by Affymetrix microarray analysis and radioactive in situ hybridization of embryonic tissue sections (E12–E14). Induction of target genes by growth factors in bone and tooth tissue was studied using in vitro experiments, including a novel method involving hanging‐drop cultures and RT‐PCR.
Results: Thirteen bone and four tooth genes were identified that are Runx2‐dependent. The identities of these genes do not significantly overlap between bone and tooth, indicating tissue specificity of several genes regulated by Runx2. Genes downregulated in bone development in Runx2 null mutants were Bambi, Bmp4, Bono1, Dkk1, Fgf receptor1, Gli1, Lef1, Patched, Prostaglandin F receptor1, Tcf1, Tgfβ1, Wnt10a, and Wnt10b. Several of these genes were induced by BMPs in bone tissue in a Runx2‐independent manner. Genes downregulated in tooth development were Dkk1, Dusp6, Enpp1, and Igfbp3. These genes were all induced by fibroblast growth factors (FGFs) in dental tissue. FGF‐induction of Dkk1 was completely dependent on Runx2 function.
Conclusions: The contrasting identities and distinctive mechanisms that stimulate the expression of Runx2‐dependent genes in bone and tooth development imply that the developmental roles of Runx2 in these separate tissues are different. In tooth development, Dkk1 may be a direct transcriptional target of Runx2. Bone genes were stimulated by BMP4 before the formation of the ossification center, suggesting that BMPs may mediate the early epithelial–mesenchymal interactions involved in bone formation.</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1359/jbmr.060413</identifier><identifier>PMID: 16813524</identifier><identifier>CODEN: JBMREJ</identifier><language>eng</language><publisher>Washington, DC: John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)</publisher><subject>Animals ; Bambi ; Biological and medical sciences ; Bmp4 ; Bone Development - physiology ; Bono1 ; Cell Communication - physiology ; Core Binding Factor Alpha 1 Subunit - deficiency ; Core Binding Factor Alpha 1 Subunit - metabolism ; Dickkopf1 ; Epithelial Cells - cytology ; Epithelial Cells - metabolism ; epithelial‐mesenchymal interactions ; Fgf receptor1 ; Fundamental and applied biological sciences. Psychology ; Gene Expression Profiling ; Gene Expression Regulation, Developmental - physiology ; Gli1 ; intramembranous ossification ; Lef1 ; mandibular bone ; Mesoderm - cytology ; Mesoderm - metabolism ; Mice ; Mice, Mutant Strains ; Neural Crest - embryology ; Oligonucleotide Array Sequence Analysis ; Patched ; Prostaglandin F receptor ; Runx2 ; Skeleton and joints ; Tcf1 ; Tgfα1 ; tooth ; Tooth - embryology ; Vertebrates: osteoarticular system, musculoskeletal system ; Wnt10a ; Wnt10b</subject><ispartof>Journal of bone and mineral research, 2006-07, Vol.21 (7), p.1034-1044</ispartof><rights>Copyright © 2006 ASBMR</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4997-c8b1c3d914ca50c843096aae146df157ccfca80affb715e93fa8921dc7a718c93</citedby><cites>FETCH-LOGICAL-c4997-c8b1c3d914ca50c843096aae146df157ccfca80affb715e93fa8921dc7a718c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1359%2Fjbmr.060413$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1359%2Fjbmr.060413$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17948023$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16813524$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>James, Martyn J</creatorcontrib><creatorcontrib>Järvinen, Elina</creatorcontrib><creatorcontrib>Wang, Xiu‐Ping</creatorcontrib><creatorcontrib>Thesleff, Irma</creatorcontrib><title>Different Roles of Runx2 During Early Neural Crest–Derived Bone and Tooth Development</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>We compared gene expression profiles between Runx2 null mutant mice and their wildtype littermates. Most Runx2‐dependent genes in bones were different from those in teeth, implying that the target genes of Runx2 are tissue‐dependent. In vitro experiments determined that Runx2 is a part of the FGF and BMP signaling pathways in tooth and bone development, respectively.
Introduction: Runx2 (Cbfa1) is expressed in the neural crest–derived mesenchyme of developing bone and tooth. Runx2 homozygous null mice lack bone through a failure in osteoblast differentiation and have arrested tooth development at the late bud stage. The aim of this study was to discover and compare the identities and the roles of Runx2 target genes in bone and tooth development.
Materials and Methods: Wildtype and Runx2−/− tissue was collected from mouse embryos, and gene expression was compared by Affymetrix microarray analysis and radioactive in situ hybridization of embryonic tissue sections (E12–E14). Induction of target genes by growth factors in bone and tooth tissue was studied using in vitro experiments, including a novel method involving hanging‐drop cultures and RT‐PCR.
Results: Thirteen bone and four tooth genes were identified that are Runx2‐dependent. The identities of these genes do not significantly overlap between bone and tooth, indicating tissue specificity of several genes regulated by Runx2. Genes downregulated in bone development in Runx2 null mutants were Bambi, Bmp4, Bono1, Dkk1, Fgf receptor1, Gli1, Lef1, Patched, Prostaglandin F receptor1, Tcf1, Tgfβ1, Wnt10a, and Wnt10b. Several of these genes were induced by BMPs in bone tissue in a Runx2‐independent manner. Genes downregulated in tooth development were Dkk1, Dusp6, Enpp1, and Igfbp3. These genes were all induced by fibroblast growth factors (FGFs) in dental tissue. FGF‐induction of Dkk1 was completely dependent on Runx2 function.
Conclusions: The contrasting identities and distinctive mechanisms that stimulate the expression of Runx2‐dependent genes in bone and tooth development imply that the developmental roles of Runx2 in these separate tissues are different. In tooth development, Dkk1 may be a direct transcriptional target of Runx2. Bone genes were stimulated by BMP4 before the formation of the ossification center, suggesting that BMPs may mediate the early epithelial–mesenchymal interactions involved in bone formation.</description><subject>Animals</subject><subject>Bambi</subject><subject>Biological and medical sciences</subject><subject>Bmp4</subject><subject>Bone Development - physiology</subject><subject>Bono1</subject><subject>Cell Communication - physiology</subject><subject>Core Binding Factor Alpha 1 Subunit - deficiency</subject><subject>Core Binding Factor Alpha 1 Subunit - metabolism</subject><subject>Dickkopf1</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - metabolism</subject><subject>epithelial‐mesenchymal interactions</subject><subject>Fgf receptor1</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Developmental - physiology</subject><subject>Gli1</subject><subject>intramembranous ossification</subject><subject>Lef1</subject><subject>mandibular bone</subject><subject>Mesoderm - cytology</subject><subject>Mesoderm - metabolism</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>Neural Crest - embryology</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Patched</subject><subject>Prostaglandin F receptor</subject><subject>Runx2</subject><subject>Skeleton and joints</subject><subject>Tcf1</subject><subject>Tgfα1</subject><subject>tooth</subject><subject>Tooth - embryology</subject><subject>Vertebrates: osteoarticular system, musculoskeletal system</subject><subject>Wnt10a</subject><subject>Wnt10b</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0M9uEzEQBnALgWgonLgjX-CCth2v_x9pUiiogBQVcVw53jFs5V2ndraQG-_AG_Ik3SiReiunOcxP34w-Ql4yOGFc2tPrVZ9PQIFg_BGZMVnzSijDHpMZGCMqEJwdkWelXAOAkko9JUds2nNZixn5vuhCwIzDhi5TxEJToMtx-F3TxZi74Qc9dzlu6Rccs4t0nrFs_v35u8Dc3WJLz9KA1A0tvUpp85Mu8BZjWvdT2nPyJLhY8MVhHpNv78-v5hfV5dcPH-fvLisvrNWVNyvmeWuZ8E6CN4KDVc4hE6oNTGrvg3cGXAgrzSRaHpyxNWu9dpoZb_kxebPPXed0M07fNX1XPMboBkxjaZRRIKWA_0JmhVWyNhN8u4c-p1Iyhmadu97lbcOg2RXe7Apv9oVP-tUhdlz12N7bQ8MTeH0ArngXQ3aD78q901YYqHdBeu9-dRG3D91sPp19XkoloWagQfM7nI2aGw</recordid><startdate>200607</startdate><enddate>200607</enddate><creator>James, Martyn J</creator><creator>Järvinen, Elina</creator><creator>Wang, Xiu‐Ping</creator><creator>Thesleff, Irma</creator><general>John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)</general><general>American Society for Bone and Mineral Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7X8</scope></search><sort><creationdate>200607</creationdate><title>Different Roles of Runx2 During Early Neural Crest–Derived Bone and Tooth Development</title><author>James, Martyn J ; Järvinen, Elina ; Wang, Xiu‐Ping ; Thesleff, Irma</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4997-c8b1c3d914ca50c843096aae146df157ccfca80affb715e93fa8921dc7a718c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Bambi</topic><topic>Biological and medical sciences</topic><topic>Bmp4</topic><topic>Bone Development - physiology</topic><topic>Bono1</topic><topic>Cell Communication - physiology</topic><topic>Core Binding Factor Alpha 1 Subunit - deficiency</topic><topic>Core Binding Factor Alpha 1 Subunit - metabolism</topic><topic>Dickkopf1</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - metabolism</topic><topic>epithelial‐mesenchymal interactions</topic><topic>Fgf receptor1</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Developmental - physiology</topic><topic>Gli1</topic><topic>intramembranous ossification</topic><topic>Lef1</topic><topic>mandibular bone</topic><topic>Mesoderm - cytology</topic><topic>Mesoderm - metabolism</topic><topic>Mice</topic><topic>Mice, Mutant Strains</topic><topic>Neural Crest - embryology</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Patched</topic><topic>Prostaglandin F receptor</topic><topic>Runx2</topic><topic>Skeleton and joints</topic><topic>Tcf1</topic><topic>Tgfα1</topic><topic>tooth</topic><topic>Tooth - embryology</topic><topic>Vertebrates: osteoarticular system, musculoskeletal system</topic><topic>Wnt10a</topic><topic>Wnt10b</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>James, Martyn J</creatorcontrib><creatorcontrib>Järvinen, Elina</creatorcontrib><creatorcontrib>Wang, Xiu‐Ping</creatorcontrib><creatorcontrib>Thesleff, Irma</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>James, Martyn J</au><au>Järvinen, Elina</au><au>Wang, Xiu‐Ping</au><au>Thesleff, Irma</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Different Roles of Runx2 During Early Neural Crest–Derived Bone and Tooth Development</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2006-07</date><risdate>2006</risdate><volume>21</volume><issue>7</issue><spage>1034</spage><epage>1044</epage><pages>1034-1044</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><coden>JBMREJ</coden><abstract>We compared gene expression profiles between Runx2 null mutant mice and their wildtype littermates. Most Runx2‐dependent genes in bones were different from those in teeth, implying that the target genes of Runx2 are tissue‐dependent. In vitro experiments determined that Runx2 is a part of the FGF and BMP signaling pathways in tooth and bone development, respectively.
Introduction: Runx2 (Cbfa1) is expressed in the neural crest–derived mesenchyme of developing bone and tooth. Runx2 homozygous null mice lack bone through a failure in osteoblast differentiation and have arrested tooth development at the late bud stage. The aim of this study was to discover and compare the identities and the roles of Runx2 target genes in bone and tooth development.
Materials and Methods: Wildtype and Runx2−/− tissue was collected from mouse embryos, and gene expression was compared by Affymetrix microarray analysis and radioactive in situ hybridization of embryonic tissue sections (E12–E14). Induction of target genes by growth factors in bone and tooth tissue was studied using in vitro experiments, including a novel method involving hanging‐drop cultures and RT‐PCR.
Results: Thirteen bone and four tooth genes were identified that are Runx2‐dependent. The identities of these genes do not significantly overlap between bone and tooth, indicating tissue specificity of several genes regulated by Runx2. Genes downregulated in bone development in Runx2 null mutants were Bambi, Bmp4, Bono1, Dkk1, Fgf receptor1, Gli1, Lef1, Patched, Prostaglandin F receptor1, Tcf1, Tgfβ1, Wnt10a, and Wnt10b. Several of these genes were induced by BMPs in bone tissue in a Runx2‐independent manner. Genes downregulated in tooth development were Dkk1, Dusp6, Enpp1, and Igfbp3. These genes were all induced by fibroblast growth factors (FGFs) in dental tissue. FGF‐induction of Dkk1 was completely dependent on Runx2 function.
Conclusions: The contrasting identities and distinctive mechanisms that stimulate the expression of Runx2‐dependent genes in bone and tooth development imply that the developmental roles of Runx2 in these separate tissues are different. In tooth development, Dkk1 may be a direct transcriptional target of Runx2. Bone genes were stimulated by BMP4 before the formation of the ossification center, suggesting that BMPs may mediate the early epithelial–mesenchymal interactions involved in bone formation.</abstract><cop>Washington, DC</cop><pub>John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)</pub><pmid>16813524</pmid><doi>10.1359/jbmr.060413</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Wiley Online Library Journals Frontfile Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Bambi Biological and medical sciences Bmp4 Bone Development - physiology Bono1 Cell Communication - physiology Core Binding Factor Alpha 1 Subunit - deficiency Core Binding Factor Alpha 1 Subunit - metabolism Dickkopf1 Epithelial Cells - cytology Epithelial Cells - metabolism epithelial‐mesenchymal interactions Fgf receptor1 Fundamental and applied biological sciences. Psychology Gene Expression Profiling Gene Expression Regulation, Developmental - physiology Gli1 intramembranous ossification Lef1 mandibular bone Mesoderm - cytology Mesoderm - metabolism Mice Mice, Mutant Strains Neural Crest - embryology Oligonucleotide Array Sequence Analysis Patched Prostaglandin F receptor Runx2 Skeleton and joints Tcf1 Tgfα1 tooth Tooth - embryology Vertebrates: osteoarticular system, musculoskeletal system Wnt10a Wnt10b |
| title | Different Roles of Runx2 During Early Neural Crest–Derived Bone and Tooth Development |
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