Skip navigation
Skip navigation

Stringent requirement of a proper level of canonical WNT signalling activity for head formation in mouse embryo

Fossat, Nicolas; Jones, Vanessa; Khoo, Poh-Lynn; Bogani, Debora; Hardy, Andrea; Steiner, Kirsten; Mukhopadhyay, Mahua; Westphal, Heiner; Nolan, Patrick; Arkell, Ruth; Tam, Patrick

Description

In mouse embryos, loss of Dickkopf-1 (DKK1) activity is associated with an ectopic activation of WNT signalling responses in the precursors of the craniofacial structures and leads to a complete truncation of the head at early organogenesis. Here, we show that ENU-induced mutations of genes coding for two WNT canonical pathway factors, the co-receptor LRP6 and the transcriptional co-activator β-catenin, also elicit an ectopic signalling response and result in loss of the rostral tissues of the...[Show more]

dc.contributor.authorFossat, Nicolas
dc.contributor.authorJones, Vanessa
dc.contributor.authorKhoo, Poh-Lynn
dc.contributor.authorBogani, Debora
dc.contributor.authorHardy, Andrea
dc.contributor.authorSteiner, Kirsten
dc.contributor.authorMukhopadhyay, Mahua
dc.contributor.authorWestphal, Heiner
dc.contributor.authorNolan, Patrick
dc.contributor.authorArkell, Ruth
dc.contributor.authorTam, Patrick
dc.date.accessioned2015-12-10T23:22:47Z
dc.identifier.issn0950-1991
dc.identifier.urihttp://hdl.handle.net/1885/66666
dc.description.abstractIn mouse embryos, loss of Dickkopf-1 (DKK1) activity is associated with an ectopic activation of WNT signalling responses in the precursors of the craniofacial structures and leads to a complete truncation of the head at early organogenesis. Here, we show that ENU-induced mutations of genes coding for two WNT canonical pathway factors, the co-receptor LRP6 and the transcriptional co-activator β-catenin, also elicit an ectopic signalling response and result in loss of the rostral tissues of the forebrain. Compound mutant embryos harbouring combinations of mutant alleles of Lrp6, Ctnnb1 and Dkk1 recapitulate the partial to complete head truncation phenotype of individual homozygous mutants. The demonstration of a synergistic interaction of Dkk1, Lrp6 and Ctnnb1 provides compelling evidence supporting the concepts that (1) stringent regulation of the level of canonical WNT signalling is necessary for head formation, (2) activity of the canonical pathway is sufficient to account for the phenotypic effects of mutations in three different components of the signal cascade and (3) rostral parts of the brain and the head are differentially more sensitive to canonical WNT signalling and their development is contingent on negative modulation of WNT signalling activity.
dc.publisherThe Company of Biologists Ltd
dc.rightsAuthor/s retain copyright
dc.sourceDevelopment
dc.subjectKeywords: beta catenin; dickkopf 1 protein; low density lipoprotein receptor related protein 6; Wnt protein; allele; article; development; embryo; forebrain; gene mutation; genotype; head formation; homozygosity; induced mutation; mouse; mouse embryo; nonhuman; phe ß-catenin; Dkk1; ENU mutant; Gene dosage; Head formation; Lrp6; Mouse; WNT signalling
dc.titleStringent requirement of a proper level of canonical WNT signalling activity for head formation in mouse embryo
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume138
dc.date.issued2011
local.identifier.absfor060103 - Cell Development, Proliferation and Death
local.identifier.absfor060403 - Developmental Genetics (incl. Sex Determination)
local.identifier.ariespublicationf2965xPUB1323
local.type.statusPublished Version
local.contributor.affiliationFossat, Nicolas, University of Sydney
local.contributor.affiliationJones, Vanessa, University of Sydney
local.contributor.affiliationKhoo, Poh-Lynn, University of Sydney
local.contributor.affiliationBogani, Debora, Medical Research Council
local.contributor.affiliationHardy, Andrea, Medical Research Council
local.contributor.affiliationSteiner, Kirsten, Children's Medical Research Institute
local.contributor.affiliationMukhopadhyay, Mahua, National Institutes of Health
local.contributor.affiliationWestphal, Heiner, National Institutes of Health
local.contributor.affiliationNolan, Patrick, Medical Research Council
local.contributor.affiliationArkell, Ruth, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationTam, Patrick, Children's Medical Research Institute
local.bibliographicCitation.issue4
local.bibliographicCitation.startpage667
local.bibliographicCitation.lastpage676
local.identifier.doi10.1242/dev.052803
local.identifier.absseo970106 - Expanding Knowledge in the Biological Sciences
dc.date.updated2016-02-24T08:12:35Z
local.identifier.scopusID2-s2.0-79951520988
local.identifier.thomsonID000286590400008
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

Download

File Description SizeFormat Image
01_Fossat_Stringent_requirement_of_a_2011.pdf2.87 MBAdobe PDF


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  19 May 2020/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator