title: Laminin alpha1 globular domains 4-5 induce fetal development but are not vital for embryonic basement membrane assembly.
abstract: During early mouse embryogenesis, each laminin (Lm) chain of the first described Lm, a heterotrimer of alpha1, beta1, and gamma1 chains (Lm-1), is essential for basement membrane (BM) assembly, which is required for pregastrulation development. Individual domains may have other functions, not necessarily structural. The cell binding C terminus of Lm alpha1 chain contains five Lm globular (LG) domains. In vitro, alpha1LG1-3 domains bind integrins, and alpha1LG4 binds dystroglycan, heparin, and sulfatides. A prevailing hypothesis is that alpha1LG4 is crucial as a structural domain for BM assembly, whereas integrin-binding sites conduct signaling. The in vivo role of alpha1LG4-5 (also called E3) has not been studied. Mice lacking alpha1LG4-5 were therefore made. Null embryos implanted, but presumptive epiblast cells failed to polarize and did not survive past day 6.5. BM components including truncated Lm alpha1 were detected in Reichert's membrane. Surprisingly, embryonic BM assembly between visceral endoderm and stem cells was normal in null embryos and in embryoid bodies of alpha1LG4-5-null embryonic stem cells. Yet, stem cells could not develop into polarized epiblast cells. Thus, alpha1LG4-5 provides vital signals for the conversion of stem cells to polarized epithelium.
authors.affiliation: Department of Cell and Molecular Biology, Lund University, 22184 Lund, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schéele
authors.forename: Mats
authors.initials: M
authors.lastname: Falk
authors.forename: Ahnders
authors.initials: A
authors.lastname: Franzén
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ellin
authors.forename: Maria
authors.initials: M
authors.lastname: Ferletta
authors.forename: Peter
authors.initials: P
authors.lastname: Lonai
authors.forename: Björn
authors.initials: B
authors.lastname: Andersson
authors.forename: Rupert
authors.initials: R
authors.lastname: Timpl
authors.forename: Erik
authors.initials: E
authors.lastname: Forsberg
authors.forename: Peter
authors.initials: P
authors.lastname: Ekblom
mesh_terms: D000818:Animals; D001483:Base Sequence; D001485:Basement Membrane / Q000502:physiology*; D001665:Binding Sites; D017931:DNA Primers; D047109:Fetal Development / Q000502:physiology*; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D016023:Integrins; D007797:Laminin; C084098:laminin A