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1477-9129136182009SepDevelopment (Cambridge, England)DevelopmentTbx1 controls cardiac neural crest cell migration during arch artery development by regulating Gbx2 expression in the pharyngeal ectoderm.317331833173-8310.1242/dev.028902Elucidating the gene regulatory networks that govern pharyngeal arch artery (PAA) development is an important goal, as such knowledge can help to identify new genes involved in cardiovascular disease. The transcription factor Tbx1 plays a vital role in PAA development and is a major contributor to cardiovascular disease associated with DiGeorge syndrome. In this report, we used various genetic approaches to reveal part of a signalling network by which Tbx1 controls PAA development in mice. We investigated the crucial role played by the homeobox-containing transcription factor Gbx2 downstream of Tbx1. We found that PAA formation requires the pharyngeal surface ectoderm as a key signalling centre from which Gbx2, in response to Tbx1, triggers essential directional cues to the adjacent cardiac neural crest cells (cNCCs) en route to the caudal PAAs. Abrogation of this signal generates cNCC patterning defects leading to PAA abnormalities. Finally, we showed that the Slit/Robo signalling pathway is activated during cNCC migration and that components of this pathway are affected in Gbx2 and Tbx1 mutant embryos at the time of PAA development. We propose that the spatiotemporal control of this tightly orchestrated network of genes participates in crucial aspects of PAA development.CalmontAmélieAMolecular Medicine Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.IvinsSarahSVan BuerenKelly LammertsKLPapangeliIrinnaIKyriakopoulouVanessaVAndrewsWilliam DWDMartinJames FJFMoonAnne MAMIllingworthElizabeth AEABassonM AlbertMAScamblerPeter JPJengR01 HD044157HDNICHD NIH HHSUnited StatesTCP04006TI_TelethonItalyR01HD044157HDNICHD NIH HHSUnited StatesG0601104MRC_Medical Research CouncilUnited KingdomR01DE/HD12324DENIDCR NIH HHSUnited StatesRG/05/013BHF_British Heart FoundationUnited Kingdom074549WT_Wellcome TrustUnited KingdomJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't
EnglandDevelopment87017440950-19910Glycoproteins0Homeodomain Proteins0Nerve Tissue Proteins0Receptors, Immunologic0T-Box Domain Proteins0Roundabout Proteins0Gbx2 protein, mouse0Tbx1 protein, mouse0slit protein, vertebrateIMAnimalsArteriesabnormalitiesanatomy & histologyembryologyBody PatterningphysiologyBranchial Regionabnormalitiesblood supplyembryologyCell MovementphysiologyEctodermanatomy & histologyembryologymetabolismEmbryo, Mammaliananatomy & histologyphysiologyGlycoproteinsmetabolismHeartembryologyHomeodomain ProteinsgeneticsmetabolismMiceMice, KnockoutNerve Tissue ProteinsmetabolismNeural CrestcytologyReceptors, ImmunologicmetabolismSignal TransductionphysiologyT-Box Domain ProteinsgeneticsmetabolismRoundabout Proteins2009825902009825902009113602010315ppublish19700621PMC273037110.1242/dev.028902136/18/3173Andrews, W., Barber, M., Hernadez-Miranda, L. R., Xian, J., Rakic, S., Sundaresan, V., Rabbitts, T. H., Pannell, R., Rabbitts, P., Thompson, H. et al. (2008). 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