Stringent requirement of a proper level of canonical WNT signalling activity for head formation in mouse embryo
| العنوان: | Stringent requirement of a proper level of canonical WNT signalling activity for head formation in mouse embryo |
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| المؤلفون: | Vanessa Jones, Patrick M. Nolan, Ruth M. Arkell, Patrick P.L. Tam, Poh-Lynn Khoo, Kirsten A. Steiner, Debora Bogani, Nicolas Fossat, Mahua Mukhopadhyay, Heiner Westphal, Andrea Hardy |
| المصدر: | Development. 138:667-676 |
| بيانات النشر: | The Company of Biologists, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Mutant, Gene mutation, Biology, Mice, Animals, Molecular Biology, Alleles, LDL-Receptor Related Proteins, beta Catenin, Genetics, Mice, Inbred BALB C, Base Sequence, Wnt signaling pathway, Gene Expression Regulation, Developmental, LRP6, LRP5, Phenotype, Wnt Proteins, DKK1, Low Density Lipoprotein Receptor-Related Protein-6, Mutation, Forebrain, Intercellular Signaling Peptides and Proteins, Head, Signal Transduction, Developmental Biology |
| الوصف: | 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 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. |
| تدمد: | 1477-9129 0950-1991 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::153b5ab3d2702ecf813140d6b027f282Test https://doi.org/10.1242/dev.052803Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....153b5ab3d2702ecf813140d6b027f282 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14779129 09501991 |
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