WNT-11 SIGNALLING, ITS ROLE IN CARDIOGENESIS AND IDENTIFICATION OF WNT/â-CATENIN PATHWAY TARGET GENES, ACTA UNIVERSITATIS OULUENSIS D Medica 1047

Wnt genes encode secreted signalling molecules that control embryonic development including\norganogenesis, while dysregulated Wnt signalling is connected to many diseases such as cancer.\nSpecifically, Wnts control a number of cellular processes such as proliferation, adhesion,\ndifferentiation and aging. Many Wnt proteins activate the canonical â-catenin signalling pathway\nthat regulates transcription of a still poorly characterized set of target genes. Wnts also transduce\ntheir signaling in cells via â-catenin-independent “non-canonical” pathways, which are not well\nunderstood. In this study, Wnt-11 signalling mechanisms in a mammalian model cell line and roles\nof Wnt-11 in heart development were analyzed in detail. In addition the aim was to identify new\nWnt target genes by direct chromatin immunoprecipitation and Affymetrix GeneChip assays in\nthe model cells exposed to Wnt-3a.\nOur studies reveal that Wnt-11 signalling coordinates the activity of key cell signalling\npathways, namely the canonical Wnt/â-catenin, the JNK/AP-1, the NF-êB and PI3K/Akt\npathways in the CHO cells. Analysis of the Wnt-11-deficient embryos revealed a crucial role in\nheart organogenesis. Wnt-11 signalling coordinates cell interactions during assembly of the\nmyocardial wall and Wnt-11 localizes the expression of N-cadherin and â-catenin to specific\ncellular domains in the embryonic ventricular cardiomyocytes. Collectively these studies reveal\nthat the mammalian Wnt-11 behaves as a non-canonical Wnt and that it is a critical factor in the\ncoordination of heart development. Specifically, it controls components of the cell adhesion\nmachinery. Analysis of the Wnt target genes revealed a highly context-dependent profile in the\nWnt-regulated genes. Several new putative target genes were discovered. Out of the candidate\nWnt target genes, Disabled-2 was identified as a potential new direct target for Wnt signalling.

ISBN-10:
978-951-42-6152-7
Kieli:
eng.
Sivumäärä:
152 s.
Tekijät:
Railo Antti
Tuotekoodi 013956
20,00 €