Cell-autonomous integrin control of Wnt and Notch signalling during somitogenesis.
Integrins act at signalling crossroads, and their interactions with other signal transduction pathways are key to the regulation of normal and pathological cell cytoarchitecture and behaviour. Here, we describe a signalling cascade that acts during the formation of the defining segmental features of the vertebrate body - the somites - in which β1-integrin activity regulates epithelialisation by controlling downstream Wnt and Notch activity crucial for somite border formation. Using in vivo transcriptional inhibition in the developing chick embryo, we show that β1-integrin in the anterior presomitic mesoderm activates canonical Wnt signalling in a cell-autonomous, `outside-inside' manner. Signalling is mediated by integrin-linked kinase (ILK), leading to modulation of glycogen synthase kinase 3β (GSK3β) phosphorylation, and activates Notch signalling in the anterior presomitic mesoderm. The two signalling pathways then cooperate to promote somite formation via cMESO1/Mesp2. Our results show that β1-integrin can regulate cell shape and tissue morphogenesis indirectly, by regulation of downstream signalling cascades.
Rallis
Charalampos
C
Developmental Genetics Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 4LY, UK.
Pinchin
Sheena M
SM
Ish-Horowicz
David
D
D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D002642:Chick Embryo; D046149:Embryo Culture Techniques; D055785:Gene Knockdown Techniques; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D038081:Organogenesis / Q000235:genetics / Q000502:physiology; D051880:Receptors, Notch / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D019170:Somites / Q000196:embryology* / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism* / Q000502:physiology
D019012:Integrin beta1; D051880:Receptors, Notch; D051153:Wnt Proteins