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Development ePress online publication date 21 Apr 2004
doi: 10.1242/dev.01112

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Research article

Compositional and structural requirements for laminin and basement membranes during mouse embryo implantation and gastrulation


Jeffrey H. Miner*, Cong Li, Jacqueline L. Mudd, Gloriosa Go, and Ann E. Sutherland
* Author for correspondence (e-mail: minerj{at}wustl.edu)

Laminins are components of all basement membranes and have well demonstrated roles in diverse developmental processes, from the peri-implantation period onwards. Laminin 1 ({alpha}1{beta}1{gamma}1) is a major laminin found at early stages of embryogenesis in both embryonic and extraembryonic basement membranes. The laminin {gamma}1 chain has been shown by targeted mutation to be required for endodermal differentiation and formation of basement membranes; Lamc1-/- embryos die within a day of implantation. We report the generation of mice lacking laminin {alpha}1 and laminin {beta}1, the remaining two laminin 1 chains. Mutagenic insertions in both Lama1 and Lamb1 were obtained in a secretory gene trap screen. Lamb1-/- embryos are similar to Lamc1-/- embryos in that they lack basement membranes and do not survive beyond embryonic day (E) 5.5. However, in Lama1-/- embryos, the embryonic basement membrane forms, the embryonic ectoderm cavitates and the parietal endoderm differentiates, apparently because laminin 10 ({alpha}5{beta}1{gamma}1) partially compensates for the absent laminin 1. However, such compensation did not occur for Reichert's membrane, which was absent, and the embryos died by E7. Overexpression of laminin {alpha}5 from a transgene improved the phenotype of Lama1-/- embryos to the point that they initiated gastrulation, but this overexpression did not rescue Reichert's membrane, and trophoblast cells did not form blood sinuses. These data suggest that both the molecular composition and the integrity of basement membranes are crucial for early developmental events.
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