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A secreted BMP antagonist, Cer1, fine tunes the spatial organization of the ureteric bud tree during mouse kidney development

2011Journal article Open access
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dc.contributor.authorChi, Lijun
dc.contributor.authorSaarela, Ulla
dc.contributor.authorRailo, Antti
dc.contributor.authorPrunskaite-Hyyrylainen, Renata
dc.contributor.authorSkovorodkin, Ilya
dc.contributor.authorAnthony, Shelagh
dc.contributor.authorKatsu, Kenjiro
dc.contributor.authorLiu, Yu
dc.contributor.authorShan, Jingdong
dc.contributor.authorSalgueiro, Ana Marisa
dc.contributor.authorBelo, Jose Antonio
dc.contributor.authorDavies, Jamie
dc.contributor.authorYokouchi, Yuji
dc.contributor.authorVainio, Seppo J.
dc.date.accessioned2018-12-07T14:53:33Z
dc.date.available2018-12-07T14:53:33Z
dc.date.issued2011
dc.description.abstractThe epithelial ureteric bud is critical for mammalian kidney development as it generates the ureter and the collecting duct system that induces nephrogenesis in dicrete locations in the kidney mesenchyme during its emergence. We show that a secreted Bmp antagonist Cerberus homologue (Cer1) fine tunes the organization of the ureteric tree during organogenesis in the mouse embryo. Both enhanced ureteric expression of Cer1 and Cer1 knock out enlarge kidney size, and these changes are associated with an altered three-dimensional structure of the ureteric tree as revealed by optical projection tomography. Enhanced Cer1 expression changes the ureteric bud branching programme so that more trifid and lateral branches rather than bifid ones develop, as seen in time-lapse organ culture. These changes may be the reasons for the modified spatial arrangement of the ureteric tree in the kidneys of Cer1+ embryos. Cer1 gain of function is associated with moderately elevated expression of Gdnf and Wnt11, which is also induced in the case of Cer1 deficiency, where Bmp4 expression is reduced, indicating the dependence of Bmp expression on Cer1. Cer1 binds at least Bmp2/4 and antagonizes Bmp signalling in cell culture. In line with this, supplementation of Bmp4 restored the ureteric bud tip number, which was reduced by Cer1+ to bring it closer to the normal, consistent with models suggesting that Bmp signalling inhibits ureteric bud development. Genetic reduction of Wnt11 inhibited the Cer1-stimulated kidney development, but Cer1 did not influence Wnt11 signalling in cell culture, although it did inhibit the Wnt3a-induced canonical Top Flash reporter to some extent. We conclude that Cer1 fine tunes the spatial organization of the ureteric tree by coordinating the activities of the growth-promoting ureteric bud signals Gndf and Wnt11 via Bmp-mediated antagonism and to some degree via the canonical Wnt signalling involved in branching.
dc.description.sponsorshipAcademy of Finland; Sigrid Juselius Foundation; Finnish Cancer Organizations; UK Medical Research Council; European Union [LSHG-CT-2004-005085, HEALTH-F5-2008-223007]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1371/journal.pone.0027676
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10400.1/11567
dc.language.isoeng
dc.peerreviewedyes
dc.publisherPublic Library of Science
dc.relationSet up and comparison of multiple stem cell approaches for kidney repair
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBone morphogenetic protein
dc.subjectRenal branching morphogenesis
dc.subjectMetanephric mesenchyme
dc.subjectEpithelial transformation
dc.subjectGene-expression
dc.subjectCerberus-Like
dc.subjectIn-Vitro
dc.subjectSignals
dc.subjectWnt
dc.subjectOrganogenesis
dc.titleA secreted BMP antagonist, Cer1, fine tunes the spatial organization of the ureteric bud tree during mouse kidney development
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleSet up and comparison of multiple stem cell approaches for kidney repair
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/223007/EU
oaire.citation.issue11
oaire.citation.startPagee27676
oaire.citation.titlePLoS ONE
oaire.citation.volume6
oaire.fundingStreamFP7
person.familyNameSalgueiro
person.familyNameBelo
person.givenNameAna Marisa
person.givenNameJosé A.
person.identifier.ciencia-idBF13-08E9-25E6
person.identifier.orcid0000-0002-9694-1029
person.identifier.orcid0000-0001-7384-0949
person.identifier.ridF-8601-2014
person.identifier.ridF-4444-2012
person.identifier.scopus-author-id15769915500
person.identifier.scopus-author-id6602141392
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
rcaap.rightsopenAccess
rcaap.typearticle
relation.isAuthorOfPublication34cfcf3e-9961-4b04-a34d-0b73c05acc07
relation.isAuthorOfPublication4bebeb48-6fac-41a9-8363-f849def5e019
relation.isAuthorOfPublication.latestForDiscovery4bebeb48-6fac-41a9-8363-f849def5e019
relation.isProjectOfPublication14e8c4f2-8b9a-47ff-8e93-a9eb5f0f8b87
relation.isProjectOfPublication.latestForDiscovery14e8c4f2-8b9a-47ff-8e93-a9eb5f0f8b87

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