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Category CDBセミナー
Date and Time 2006-10-25 09:30 - 10:30
Venue Auditorium C1F
Speaker Patrick P.L. Tam
Affiliation Embryology Unit, Children's Medical Research Institute and Faculty of Medicine, The University of Sydney
Title Signalling and Tissue Interactions for Anterior Morphogenesis in the Mouse
Poster click here to download(PDF)
Host Shinichi Aizawa
Summary Morphogenesis of the craniofacial structures begins with the specification of the anterior-posterior polarity of the embryo prior to the onset of gastrulation. This patterning activity is reinforced by a putatively graded level of WNT signalling that is generating by the interaction of the activities of agonists in the posterior and the antagonists in the anterior germ layer tissues. By examining the phenotype of compound mutant Dkk1;Wnt3 and Dkk1;Gsc mice, we demonstrate a requirement for the modulation of WNT signal at distinct times and sites during development. The manifestation of enhanced as well as novel mutant phenotypes in embryos harbouring loss of function mutations of Dkk1 and Wnt3 reveals a genetic interaction between the activities of these genes in head morphogenesis. Surprisingly, a reduced Wnt3 activity over the Dkk1-null background may lead to an amelioration of forebrain and facial defects in the Dkk1-/-;Wnt3+/- embryo. This finding suggests that Wnt3 plays a role at the initial phase of anterior morphogenesis and this early action has a lasting impact on craniofacial development. Analysis of the genetic interaction of Dkk1 and Gsc revealed a dosage-related requirement of gene functions most likely in the prechordal mesoderm and the foregut endoderm during anterior morphogenesis. The phenotypic impact of combined loss of Gsc and Dkk1 activities is consistent with a role of Gsc in the modulation of WNT signalling activity.
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