abnormal wnt and pi3kinase signaling in the malformed intestine of lama5 deficient mice异常wnt和pi3kinase信号lama5缺陷小鼠的小肠畸形.pdfVIP

Abnormal Wnt and PI3Kinase Signaling in the Malformed Intestine of lama5 Deficient Mice ´ ´ 1.¤ ´ 1. ¨ 1 2 1 Lea Ritie , Caroline Spenle , Joel Lacroute , Anne-Laure Bolcato-Bellemin , Olivier Lefebvre , 3 3 1 1 ` 1 Christine Bole-Feysot , Bernard Jost , Annick Klein , Christiane Arnold , Michele Kedinger , 1 1 1 Dominique Bagnard , Gertraud Orend , Patricia Simon-Assmann * 1 Inserm, U682, Strasbourg, France; Univ de Strasbourg, France, 2 Polyplus-transfection, Illkirch, France, 3 Microarray and Sequencing Platform, IGBMC, Illkirch, France Abstract Laminins are major constituents of basement membranes and are essential for tissue homeostasis. Laminin-511 is highly expressed in the intestine and its absence causes severe malformation of the intestine and embryonic lethality. To understand the mechanistic role of laminin-511 in tissue homeostasis, we used RNA profiling of embryonic intestinal tissue of lama5 knockout mice and identified a lama5 specific gene expression signature. By combining cell culture experiments with mediated knockdown approaches, we provide a mechanistic link between laminin a5 gene deficiency and the physiological phenotype. We show that laminin a5 plays a crucial role in both epithelial and mesenchymal cell behavior by inhibiting Wnt and activating PI3K signaling. We conclude that conflicting signals are elicited in the absence of lama5, which alter cell adhesion, migration as well as epithelia