Sox9b is a key regulator of pancreaticobiliary ductal system development
The pancreaticobiliary ductal system connects the liver and pancreas to the intestine. It is composed of the hepatopancreatic ductal (HPD) system as well as the intrahepatic biliary ducts and the intrapancreatic ducts. Despite its physiological importance, the development of the pancreaticobiliary d...
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| creator | Delous, Marion Yin, Chunyue Shin, Donghun Ninov, Nikolay Debrito Carten, Juliana Pan, Luyuan Ma, Taylur P Farber, Steven A Moens, Cecilia B Stainier, Didier Y R |
| description | The pancreaticobiliary ductal system connects the liver and pancreas to the intestine. It is composed of the hepatopancreatic ductal (HPD) system as well as the intrahepatic biliary ducts and the intrapancreatic ducts. Despite its physiological importance, the development of the pancreaticobiliary ductal system remains poorly understood. The SRY-related transcription factor SOX9 is expressed in the mammalian pancreaticobiliary ductal system, but the perinatal lethality of Sox9 heterozygous mice makes loss-of-function analyses challenging. We turned to the zebrafish to assess the role of SOX9 in pancreaticobiliary ductal system development. We first show that zebrafish sox9b recapitulates the expression pattern of mouse Sox9 in the pancreaticobiliary ductal system and use a nonsense allele of sox9b, sox9b(fh313), to dissect its function in the morphogenesis of this structure. Strikingly, sox9b(fh313) homozygous mutants survive to adulthood and exhibit cholestasis associated with hepatic and pancreatic duct proliferation, cyst formation, and fibrosis. Analysis of sox9b(fh313) mutant embryos and larvae reveals that the HPD cells appear to mis-differentiate towards hepatic and/or pancreatic fates, resulting in a dysmorphic structure. The intrahepatic biliary cells are specified but fail to assemble into a functional network. Similarly, intrapancreatic duct formation is severely impaired in sox9b(fh313) mutants, while the embryonic endocrine and acinar compartments appear unaffected. The defects in the intrahepatic and intrapancreatic ducts of sox9b(fh313) mutants worsen during larval and juvenile stages, prompting the adult phenotype. We further show that Sox9b interacts with Notch signaling to regulate intrahepatic biliary network formation: sox9b expression is positively regulated by Notch signaling, while Sox9b function is required to maintain Notch signaling in the intrahepatic biliary cells. Together, these data reveal key roles for SOX9 in the morphogenesis of the pancreaticobiliary ductal system, and they cast human Sox9 as a candidate gene for pancreaticobiliary duct malformation-related pathologies. |
| doi_str_mv | 10.1371/journal.pgen.1002754 |
| format | Article |
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It is composed of the hepatopancreatic ductal (HPD) system as well as the intrahepatic biliary ducts and the intrapancreatic ducts. Despite its physiological importance, the development of the pancreaticobiliary ductal system remains poorly understood. The SRY-related transcription factor SOX9 is expressed in the mammalian pancreaticobiliary ductal system, but the perinatal lethality of Sox9 heterozygous mice makes loss-of-function analyses challenging. We turned to the zebrafish to assess the role of SOX9 in pancreaticobiliary ductal system development. We first show that zebrafish sox9b recapitulates the expression pattern of mouse Sox9 in the pancreaticobiliary ductal system and use a nonsense allele of sox9b, sox9b(fh313), to dissect its function in the morphogenesis of this structure. Strikingly, sox9b(fh313) homozygous mutants survive to adulthood and exhibit cholestasis associated with hepatic and pancreatic duct proliferation, cyst formation, and fibrosis. Analysis of sox9b(fh313) mutant embryos and larvae reveals that the HPD cells appear to mis-differentiate towards hepatic and/or pancreatic fates, resulting in a dysmorphic structure. The intrahepatic biliary cells are specified but fail to assemble into a functional network. Similarly, intrapancreatic duct formation is severely impaired in sox9b(fh313) mutants, while the embryonic endocrine and acinar compartments appear unaffected. The defects in the intrahepatic and intrapancreatic ducts of sox9b(fh313) mutants worsen during larval and juvenile stages, prompting the adult phenotype. We further show that Sox9b interacts with Notch signaling to regulate intrahepatic biliary network formation: sox9b expression is positively regulated by Notch signaling, while Sox9b function is required to maintain Notch signaling in the intrahepatic biliary cells. Together, these data reveal key roles for SOX9 in the morphogenesis of the pancreaticobiliary ductal system, and they cast human Sox9 as a candidate gene for pancreaticobiliary duct malformation-related pathologies.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1002754</identifier><identifier>PMID: 22719264</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Bile Ducts, Intrahepatic - embryology ; Bile Ducts, Intrahepatic - growth & development ; Bile Ducts, Intrahepatic - metabolism ; Biology ; Charitable foundations ; Codon, Nonsense ; Defects ; Gallbladder ; Gallbladder diseases ; Gene Expression Regulation, Developmental ; Genetic aspects ; Liver - embryology ; Liver - growth & development ; Liver - metabolism ; Morphogenesis - genetics ; Pancreas ; Pancreas - embryology ; Pancreas - growth & development ; Pancreas - metabolism ; Physiological aspects ; Receptors, Notch - genetics ; Receptors, Notch - metabolism ; Rodents ; Signal Transduction ; SOX9 Transcription Factor - genetics ; SOX9 Transcription Factor - metabolism ; Systems development ; Transcription factors ; Zebra fish ; Zebrafish - embryology ; Zebrafish - genetics ; Zebrafish Proteins - genetics ; Zebrafish Proteins - metabolism</subject><ispartof>PLoS genetics, 2012-06, Vol.8 (6), p.e1002754-e1002754</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Delous et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Delous M, Yin C, Shin D, Ninov N, Debrito Carten J, et al. (2012) sox9b Is a Key Regulator of Pancreaticobiliary Ductal System Development. PLoS Genet 8(6): e1002754. doi:10.1371/journal.pgen.1002754</rights><rights>Delous et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c792t-217efcf16e93ea601ccff94bdd74dd487c58de7ebd5e7c3d953581e1cac5e9fb3</citedby><cites>FETCH-LOGICAL-c792t-217efcf16e93ea601ccff94bdd74dd487c58de7ebd5e7c3d953581e1cac5e9fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375260/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375260/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22719264$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Delous, Marion</creatorcontrib><creatorcontrib>Yin, Chunyue</creatorcontrib><creatorcontrib>Shin, Donghun</creatorcontrib><creatorcontrib>Ninov, Nikolay</creatorcontrib><creatorcontrib>Debrito Carten, Juliana</creatorcontrib><creatorcontrib>Pan, Luyuan</creatorcontrib><creatorcontrib>Ma, Taylur P</creatorcontrib><creatorcontrib>Farber, Steven A</creatorcontrib><creatorcontrib>Moens, Cecilia B</creatorcontrib><creatorcontrib>Stainier, Didier Y R</creatorcontrib><title>Sox9b is a key regulator of pancreaticobiliary ductal system development</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>The pancreaticobiliary ductal system connects the liver and pancreas to the intestine. It is composed of the hepatopancreatic ductal (HPD) system as well as the intrahepatic biliary ducts and the intrapancreatic ducts. Despite its physiological importance, the development of the pancreaticobiliary ductal system remains poorly understood. The SRY-related transcription factor SOX9 is expressed in the mammalian pancreaticobiliary ductal system, but the perinatal lethality of Sox9 heterozygous mice makes loss-of-function analyses challenging. We turned to the zebrafish to assess the role of SOX9 in pancreaticobiliary ductal system development. We first show that zebrafish sox9b recapitulates the expression pattern of mouse Sox9 in the pancreaticobiliary ductal system and use a nonsense allele of sox9b, sox9b(fh313), to dissect its function in the morphogenesis of this structure. Strikingly, sox9b(fh313) homozygous mutants survive to adulthood and exhibit cholestasis associated with hepatic and pancreatic duct proliferation, cyst formation, and fibrosis. Analysis of sox9b(fh313) mutant embryos and larvae reveals that the HPD cells appear to mis-differentiate towards hepatic and/or pancreatic fates, resulting in a dysmorphic structure. The intrahepatic biliary cells are specified but fail to assemble into a functional network. Similarly, intrapancreatic duct formation is severely impaired in sox9b(fh313) mutants, while the embryonic endocrine and acinar compartments appear unaffected. The defects in the intrahepatic and intrapancreatic ducts of sox9b(fh313) mutants worsen during larval and juvenile stages, prompting the adult phenotype. We further show that Sox9b interacts with Notch signaling to regulate intrahepatic biliary network formation: sox9b expression is positively regulated by Notch signaling, while Sox9b function is required to maintain Notch signaling in the intrahepatic biliary cells. Together, these data reveal key roles for SOX9 in the morphogenesis of the pancreaticobiliary ductal system, and they cast human Sox9 as a candidate gene for pancreaticobiliary duct malformation-related pathologies.</description><subject>Animals</subject><subject>Bile Ducts, Intrahepatic - embryology</subject><subject>Bile Ducts, Intrahepatic - growth & development</subject><subject>Bile Ducts, Intrahepatic - metabolism</subject><subject>Biology</subject><subject>Charitable foundations</subject><subject>Codon, Nonsense</subject><subject>Defects</subject><subject>Gallbladder</subject><subject>Gallbladder diseases</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Genetic aspects</subject><subject>Liver - embryology</subject><subject>Liver - growth & development</subject><subject>Liver - metabolism</subject><subject>Morphogenesis - genetics</subject><subject>Pancreas</subject><subject>Pancreas - embryology</subject><subject>Pancreas - growth & development</subject><subject>Pancreas - metabolism</subject><subject>Physiological aspects</subject><subject>Receptors, Notch - genetics</subject><subject>Receptors, Notch - metabolism</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>SOX9 Transcription Factor - genetics</subject><subject>SOX9 Transcription Factor - metabolism</subject><subject>Systems development</subject><subject>Transcription factors</subject><subject>Zebra fish</subject><subject>Zebrafish - embryology</subject><subject>Zebrafish - genetics</subject><subject>Zebrafish Proteins - genetics</subject><subject>Zebrafish Proteins - metabolism</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqVk1FrFDEQxxdRbD39BqILgujDnckm2ey-CKWoPSgWrPoasslkb2t2c02ypfftzXnXcit9UPKQMPnNzH9mmCx7idECE44_XLnRD9Iu1i0MC4xQwRl9lB1jxsicU0QfH7yPsmchXCFEWFXzp9lRUXBcFyU9zs4u3W3d5F3IZf4LNrmHdrQyOp87k6_loDzI2CnXdLaTfpPrUUVp87AJEfpcww1Yt-5hiM-zJ0baAC_29yz78fnT99Oz-fnFl-Xpyflc8bqI8wJzMMrgEmoCskRYKWNq2mjNqda04opVGjg0mgFXRNcsacaAlVQMatOQWfZ6F3dtXRD7JgSBCSaMVlWNErHcEdrJK7H2XZ-ECyc78cfgfCukTzVZEESWoGSDK6UYTYlkXTBTFbQ0hdIqSZxlH_fZxqaHZBqil3YSdPozdCvRuhtBCGdFuRXzbh_Au-sRQhR9FxRYKwdwY9KNClxXFJU8oW_-Qh-ubk-1MhXQDcalvGobVJwQRAniFaWJWjxApaOhT9McwHTJPnF4P3FITITb2MoxBLG8_PYf7Nd_Zy9-Ttm3B-wKpI2r4OwYOzeEKUh3oPIuBA_mfiAYie1y3HVObJdD7Jcjub06HOa90902kN-9HwnM</recordid><startdate>20120601</startdate><enddate>20120601</enddate><creator>Delous, Marion</creator><creator>Yin, Chunyue</creator><creator>Shin, Donghun</creator><creator>Ninov, Nikolay</creator><creator>Debrito Carten, Juliana</creator><creator>Pan, Luyuan</creator><creator>Ma, Taylur P</creator><creator>Farber, Steven A</creator><creator>Moens, Cecilia B</creator><creator>Stainier, Didier Y R</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120601</creationdate><title>Sox9b is a key regulator of pancreaticobiliary ductal system development</title><author>Delous, Marion ; Yin, Chunyue ; Shin, Donghun ; Ninov, Nikolay ; Debrito Carten, Juliana ; Pan, Luyuan ; Ma, Taylur P ; Farber, Steven A ; Moens, Cecilia B ; Stainier, Didier Y R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c792t-217efcf16e93ea601ccff94bdd74dd487c58de7ebd5e7c3d953581e1cac5e9fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Bile Ducts, Intrahepatic - embryology</topic><topic>Bile Ducts, Intrahepatic - growth & development</topic><topic>Bile Ducts, Intrahepatic - metabolism</topic><topic>Biology</topic><topic>Charitable foundations</topic><topic>Codon, Nonsense</topic><topic>Defects</topic><topic>Gallbladder</topic><topic>Gallbladder diseases</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genetic aspects</topic><topic>Liver - embryology</topic><topic>Liver - growth & development</topic><topic>Liver - metabolism</topic><topic>Morphogenesis - genetics</topic><topic>Pancreas</topic><topic>Pancreas - embryology</topic><topic>Pancreas - growth & development</topic><topic>Pancreas - metabolism</topic><topic>Physiological aspects</topic><topic>Receptors, Notch - genetics</topic><topic>Receptors, Notch - metabolism</topic><topic>Rodents</topic><topic>Signal Transduction</topic><topic>SOX9 Transcription Factor - genetics</topic><topic>SOX9 Transcription Factor - metabolism</topic><topic>Systems development</topic><topic>Transcription factors</topic><topic>Zebra fish</topic><topic>Zebrafish - embryology</topic><topic>Zebrafish - genetics</topic><topic>Zebrafish Proteins - genetics</topic><topic>Zebrafish Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Delous, Marion</creatorcontrib><creatorcontrib>Yin, Chunyue</creatorcontrib><creatorcontrib>Shin, Donghun</creatorcontrib><creatorcontrib>Ninov, Nikolay</creatorcontrib><creatorcontrib>Debrito Carten, Juliana</creatorcontrib><creatorcontrib>Pan, Luyuan</creatorcontrib><creatorcontrib>Ma, Taylur P</creatorcontrib><creatorcontrib>Farber, Steven A</creatorcontrib><creatorcontrib>Moens, Cecilia B</creatorcontrib><creatorcontrib>Stainier, Didier Y R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Delous, Marion</au><au>Yin, Chunyue</au><au>Shin, Donghun</au><au>Ninov, Nikolay</au><au>Debrito Carten, Juliana</au><au>Pan, Luyuan</au><au>Ma, Taylur P</au><au>Farber, Steven A</au><au>Moens, Cecilia B</au><au>Stainier, Didier Y R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sox9b is a key regulator of pancreaticobiliary ductal system development</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2012-06-01</date><risdate>2012</risdate><volume>8</volume><issue>6</issue><spage>e1002754</spage><epage>e1002754</epage><pages>e1002754-e1002754</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>The pancreaticobiliary ductal system connects the liver and pancreas to the intestine. It is composed of the hepatopancreatic ductal (HPD) system as well as the intrahepatic biliary ducts and the intrapancreatic ducts. Despite its physiological importance, the development of the pancreaticobiliary ductal system remains poorly understood. The SRY-related transcription factor SOX9 is expressed in the mammalian pancreaticobiliary ductal system, but the perinatal lethality of Sox9 heterozygous mice makes loss-of-function analyses challenging. We turned to the zebrafish to assess the role of SOX9 in pancreaticobiliary ductal system development. We first show that zebrafish sox9b recapitulates the expression pattern of mouse Sox9 in the pancreaticobiliary ductal system and use a nonsense allele of sox9b, sox9b(fh313), to dissect its function in the morphogenesis of this structure. Strikingly, sox9b(fh313) homozygous mutants survive to adulthood and exhibit cholestasis associated with hepatic and pancreatic duct proliferation, cyst formation, and fibrosis. Analysis of sox9b(fh313) mutant embryos and larvae reveals that the HPD cells appear to mis-differentiate towards hepatic and/or pancreatic fates, resulting in a dysmorphic structure. The intrahepatic biliary cells are specified but fail to assemble into a functional network. Similarly, intrapancreatic duct formation is severely impaired in sox9b(fh313) mutants, while the embryonic endocrine and acinar compartments appear unaffected. The defects in the intrahepatic and intrapancreatic ducts of sox9b(fh313) mutants worsen during larval and juvenile stages, prompting the adult phenotype. We further show that Sox9b interacts with Notch signaling to regulate intrahepatic biliary network formation: sox9b expression is positively regulated by Notch signaling, while Sox9b function is required to maintain Notch signaling in the intrahepatic biliary cells. Together, these data reveal key roles for SOX9 in the morphogenesis of the pancreaticobiliary ductal system, and they cast human Sox9 as a candidate gene for pancreaticobiliary duct malformation-related pathologies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22719264</pmid><doi>10.1371/journal.pgen.1002754</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1553-7404 |
| ispartof | PLoS genetics, 2012-06, Vol.8 (6), p.e1002754-e1002754 |
| issn | 1553-7404 1553-7390 1553-7404 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Public Library of Science (PLoS) |
| subjects | Animals Bile Ducts, Intrahepatic - embryology Bile Ducts, Intrahepatic - growth & development Bile Ducts, Intrahepatic - metabolism Biology Charitable foundations Codon, Nonsense Defects Gallbladder Gallbladder diseases Gene Expression Regulation, Developmental Genetic aspects Liver - embryology Liver - growth & development Liver - metabolism Morphogenesis - genetics Pancreas Pancreas - embryology Pancreas - growth & development Pancreas - metabolism Physiological aspects Receptors, Notch - genetics Receptors, Notch - metabolism Rodents Signal Transduction SOX9 Transcription Factor - genetics SOX9 Transcription Factor - metabolism Systems development Transcription factors Zebra fish Zebrafish - embryology Zebrafish - genetics Zebrafish Proteins - genetics Zebrafish Proteins - metabolism |
| title | Sox9b is a key regulator of pancreaticobiliary ductal system development |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T14%3A22%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Sox9b%20is%20a%20key%20regulator%20of%20pancreaticobiliary%20ductal%20system%20development&rft.jtitle=PLoS%20genetics&rft.au=Delous,%20Marion&rft.date=2012-06-01&rft.volume=8&rft.issue=6&rft.spage=e1002754&rft.epage=e1002754&rft.pages=e1002754-e1002754&rft.issn=1553-7404&rft.eissn=1553-7404&rft_id=info:doi/10.1371/journal.pgen.1002754&rft_dat=%3Cgale_plos_%3EA304307844%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1313548890&rft_id=info:pmid/22719264&rft_galeid=A304307844&rft_doaj_id=oai_doaj_org_article_3a6ecab18cc54358a925f8246f2cdce9&rfr_iscdi=true |