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Conference Paper: Analysis of craniofacial defects in Six1/Eya1-associated Branchio-Oto-Renal Syndrome

TitleAnalysis of craniofacial defects in Six1/Eya1-associated Branchio-Oto-Renal Syndrome
Authors
Issue Date2013
PublisherThe International Society of Developmental Biologists (ISDB). The Conference's web site is located at http://www.inb.unam.mx/isdb/
Citation
The 17th International Congress of the International Society of Developmental Biologists (ISDB 2013), Cancun, Mexico, 16-20 June 2013. In Conference Abstracts, 2013, p. 58-59, abstract no. 205 How to Cite?
AbstractBranchio-Oto-Renal (BOR) syndrome patients exhibit craniofacial and renal anomalies as well as deafness. BOR syndrome is caused by mutations in Six1 or Eya1, both of which regulate cell proliferation and differentiation. The molecular mechanism underlying the craniofacial and branchial arch (BA) defects in BOR syndrome is unclear. We have found that Hoxb3 is up-regulated in the second branchial arch (BA2) of Six1-/- mutants. Moreover, Hoxb3 over-expression in transgenic mice leads to BA abnormalities which are similar to the BA defects in Six1-/- or Eya1-/- mutants, suggesting a regulatory relationship among Six1, Eya1 and Hoxb3 genes. The aim of this study is to investigate the molecular mechanism underlying abnormal BA development in BOR syndrome using Six1 and Eya1 mutant mice. Two potential Six1 binding sites were identified on the Hoxb3 gene. In vitro and in vivo Chromatin IP assays showed that Six1 could directly bind to one of the sites specifically. Furthermore, using a chick in ovo luciferase assay we showed that Six1 could suppress gene expression through one of the specific binding sites. On the other hand, in Six1-/- mutants, we found that the Notch ligand Jag1 was up-regulated in BA2. Similarly, in Hoxb3 transgenic mice, ectopic expression of Jag1 could be also detected in BA2. To investigate the activation of Notch signaling pathway, we found that Notch intracellular domain (NICD), a direct indicator of Notch pathway activation, was up-regulated in BAs of Six1-/-; Eya1-/- double mutants. Our results indicate that Hoxb3 and Notch signaling pathway are involved in mediating the craniofacial defects of Six1/Eya1-associated Branchio-Oto-Renal Syndrome.
Description17th ISDB 2013 cum 72nd Annual Meeting of the Society for Developmental Biology, 7th Latin American Society of Developmental Biology Meeting and 11th Congreso de la Sociedad Mexicana de Biologia del Desarrollo.
Poster Session I - Morphogenesis: 205/B101
Persistent Identifierhttp://hdl.handle.net/10722/184927

 

DC FieldValueLanguage
dc.contributor.authorZhang, Hen_US
dc.contributor.authorWong, EYMen_US
dc.contributor.authorTsang, SLen_US
dc.contributor.authorXu, PXen_US
dc.contributor.authorSham, MHen_US
dc.date.accessioned2013-07-15T10:18:26Z-
dc.date.available2013-07-15T10:18:26Z-
dc.date.issued2013en_US
dc.identifier.citationThe 17th International Congress of the International Society of Developmental Biologists (ISDB 2013), Cancun, Mexico, 16-20 June 2013. In Conference Abstracts, 2013, p. 58-59, abstract no. 205en_US
dc.identifier.urihttp://hdl.handle.net/10722/184927-
dc.description17th ISDB 2013 cum 72nd Annual Meeting of the Society for Developmental Biology, 7th Latin American Society of Developmental Biology Meeting and 11th Congreso de la Sociedad Mexicana de Biologia del Desarrollo.-
dc.descriptionPoster Session I - Morphogenesis: 205/B101-
dc.description.abstractBranchio-Oto-Renal (BOR) syndrome patients exhibit craniofacial and renal anomalies as well as deafness. BOR syndrome is caused by mutations in Six1 or Eya1, both of which regulate cell proliferation and differentiation. The molecular mechanism underlying the craniofacial and branchial arch (BA) defects in BOR syndrome is unclear. We have found that Hoxb3 is up-regulated in the second branchial arch (BA2) of Six1-/- mutants. Moreover, Hoxb3 over-expression in transgenic mice leads to BA abnormalities which are similar to the BA defects in Six1-/- or Eya1-/- mutants, suggesting a regulatory relationship among Six1, Eya1 and Hoxb3 genes. The aim of this study is to investigate the molecular mechanism underlying abnormal BA development in BOR syndrome using Six1 and Eya1 mutant mice. Two potential Six1 binding sites were identified on the Hoxb3 gene. In vitro and in vivo Chromatin IP assays showed that Six1 could directly bind to one of the sites specifically. Furthermore, using a chick in ovo luciferase assay we showed that Six1 could suppress gene expression through one of the specific binding sites. On the other hand, in Six1-/- mutants, we found that the Notch ligand Jag1 was up-regulated in BA2. Similarly, in Hoxb3 transgenic mice, ectopic expression of Jag1 could be also detected in BA2. To investigate the activation of Notch signaling pathway, we found that Notch intracellular domain (NICD), a direct indicator of Notch pathway activation, was up-regulated in BAs of Six1-/-; Eya1-/- double mutants. Our results indicate that Hoxb3 and Notch signaling pathway are involved in mediating the craniofacial defects of Six1/Eya1-associated Branchio-Oto-Renal Syndrome.-
dc.languageengen_US
dc.publisherThe International Society of Developmental Biologists (ISDB). The Conference's web site is located at http://www.inb.unam.mx/isdb/-
dc.relation.ispartofInternational Congress of the International Society of Developmental Biologists, ISDB 2013en_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleAnalysis of craniofacial defects in Six1/Eya1-associated Branchio-Oto-Renal Syndromeen_US
dc.typeConference_Paperen_US
dc.identifier.emailWong, EYM: elainewg@hku.hken_US
dc.identifier.emailTsang, SL: sltsang@hku.hken_US
dc.identifier.emailSham, MH: mhsham@hku.hken_US
dc.identifier.authorityWong, EYM=rp01718en_US
dc.identifier.authoritySham, MH=rp00380en_US
dc.description.naturepostprint-
dc.identifier.hkuros216498en_US
dc.identifier.hkuros223639-
dc.identifier.spage58, abstract no. 205-
dc.identifier.epage59-
dc.publisher.placeMexico-

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