Laminin alpha5 chain is required for intestinal smooth muscle development.
Laminins (comprised of alpha, beta, and gamma chains) are heterotrimeric glycoproteins integral to all basement membranes. The function of the laminin alpha5 chain in the developing intestine was defined by analysing laminin alpha5(-/-) mutants and by grafting experiments. We show that laminin alpha5 plays a major role in smooth muscle organisation and differentiation, as excessive folding of intestinal loops and delay in the expression of specific markers are observed in laminin alpha5(-/-) mice. In the subepithelial basement membrane, loss of alpha5 expression was paralleled by ectopic or accelerated deposition of laminin alpha2 and alpha4 chains; this may explain why no obvious defects were observed in the villous form and enterocytic differentiation. This compensation process is attributable to mesenchyme-derived molecules as assessed by chick/mouse alpha5(-/-) grafted associations. Lack of the laminin alpha5 chain was accompanied by a decrease in epithelial alpha3beta1 integrin receptor expression adjacent to the epithelial basement membrane and of Lutheran blood group glycoprotein in the smooth muscle cells, indicating that these receptors are likely mediating interactions with laminin alpha5-containing molecules. Taken together, the data indicate that the laminin alpha5 chain is essential for normal development of the intestinal smooth muscle and point to possible mesenchyme-derived compensation to promote normal intestinal morphogenesis when laminin alpha5 is absent.
Bolcato-Bellemin
Anne Laure
AL
INSERM U381, Ontogenèse et Pathologie du Système Digestif, Avenue Molière, Strasbourg, France.
Lefebvre
Olivier
O
Arnold
Christiane
C
Sorokin
Lydia
L
Miner
Jeffrey H
JH
Kedinger
Michèle
M
Simon-Assmann
Patricia
P
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D015815:Cell Adhesion Molecules; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000002:abnormalities / Q000196:embryology*; D007797:Laminin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008188:Lutheran Blood-Group System; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009130:Muscle, Smooth / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism / Q000637:transplantation; D019737:Transplants
C477645:Bcam protein, mouse; D015815:Cell Adhesion Molecules; D039201:Integrin alpha3beta1; C501370:Lama4 protein, mouse; D007797:Laminin; D008188:Lutheran Blood-Group System; D008562:Membrane Glycoproteins; C097043:laminin alpha5; C058783:laminin beta2