Lefebvre O, Sorokin L, Kedinger M, Simon-Assmann P
INSERM U.381, 3 Avenue Molière, Strasbourg, 67200, France.
Dev Biol. 1999 Jun 1;210(1):135-50. doi: 10.1006/dbio.1999.9270.
Laminins are extracellular matrix glycoproteins that are involved in various cellular functions, including adhesion, proliferation, and differentiation. In this study, we examine the expression patterns and the cellular origins of the laminin alpha2, alpha4, and alpha5 chains in the developing mouse intestine and in in vitro mouse/chick or chick/mouse interspecies hybrid intestines. In situ hybridization and Northern blot analysis revealed that mRNA levels for all three laminin alpha chains are highest in the fetal intestine undergoing intense morphogenetic movements. Laminin alpha4 mRNA and polypeptide are associated with mesenchyme-derived cell populations such as endothelium and smooth muscle. In contrast, laminin alpha2 and alpha5 chains participate in the structural organization of the subepithelial basement membrane and, in the mature intestine, show a complementary pattern of expression. All three laminin alpha chains occur in the smooth muscle basement membrane, with a differential expression of laminin alpha5 chain in the circular and longitudinal smooth muscle layers. The cellular origin of laminin alpha2 and alpha5 chains found in the subepithelial cell basement membrane was studied by immunocytochemical analysis of mouse/chick or chick/mouse interspecies hybrid intestines at various stages of development using mouse-specific antibodies. Laminin alpha2 was found to be deposited into the basement membrane exclusively by mesenchymal cells, while the laminin alpha5 chain was deposited by both epithelial and mesenchymal cells in an apparently developmentally regulated pattern. We conclude that (1) multiple laminin alpha chains are expressed in the intestine, implying specific roles for individual laminin isoforms during intestinal development, and (2) reciprocal epithelial/mesenchymal interactions are essential for the formation of a structured subepithelial basement membrane.
层粘连蛋白是细胞外基质糖蛋白，参与多种细胞功能，包括黏附、增殖和分化。在本研究中，我们检测了层粘连蛋白α2、α4和α5链在发育中的小鼠肠道以及体外小鼠/鸡或鸡/小鼠种间杂交肠道中的表达模式和细胞来源。原位杂交和Northern印迹分析显示，所有三种层粘连蛋白α链的mRNA水平在经历强烈形态发生运动的胎儿肠道中最高。层粘连蛋白α4 mRNA和多肽与间充质来源的细胞群体相关，如内皮细胞和平滑肌细胞。相比之下，层粘连蛋白α2和α5链参与上皮下基底膜的结构组织，并且在成熟肠道中呈现互补的表达模式。所有三种层粘连蛋白α链都存在于平滑肌基底膜中，层粘连蛋白α5链在环形和纵形平滑肌层中存在差异表达。通过使用小鼠特异性抗体对处于不同发育阶段的小鼠/鸡或鸡/小鼠种间杂交肠道进行免疫细胞化学分析，研究了上皮下细胞基底膜中层粘连蛋白α2和α5链的细胞来源。发现层粘连蛋白α2仅由间充质细胞沉积到基底膜中，而层粘连蛋白α5链由上皮细胞和间充质细胞以明显受发育调控的模式沉积。我们得出结论：（1）多种层粘连蛋白α链在肠道中表达，这意味着单个层粘连蛋白异构体在肠道发育过程中具有特定作用；（2）上皮/间充质的相互作用对于形成结构化的上皮下基底膜至关重要。
