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

Abstract

Laminins are components of all basement membranes and have well demonstrated roles in diverse developmental processes, from the peri-implantation period onwards. Laminin 1 (α1β1γ1) is a major laminin found at early stages of embryogenesis in both embryonic and extraembryonic basement membranes. The laminin γ1 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 lamininα1 and laminin β1, 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 (α5β1γ1) 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 α5 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.

laminin alpha 1gene is essential for normal lens development in zebrafish

“…This condition is different from the phenotype reported in Lama1-/- knockout mice [15]. The Lama-/- null mice die prenatally around day 7 post coitus (pc) while the embryos that are deficient in either β1 or γ1 laminin chains do not survive past day 5.5 pc, which is the blastula stages in mice [15]. The laminin-1 is first detected around the 16-cell stage in mice and present in the two basement membranes formed before gastrulation.…”

“…The laminin-1 is first detected around the 16-cell stage in mice and present in the two basement membranes formed before gastrulation. Mammalian embryos deficient in any component of laminin-1 (α1β1γ1) survive implantation but die before gastrulation indicating to the critical role of laminin-1 in this process [15,49]. In zebrafish, implantation does not occur as embryogenesis occurs ex utero .…”

“…Laminin-1 is detected in most embryonic tissues during early morphogenesis and remains present as a major epithelial laminin in some adult tissues [2,11-13]. Mice that are deficient in any chain that composes laminin-1 (α1β1γ1) die during the early postimplantation period with the Lama1 -/- phenotype being the mildest of the three genes deleted [14,15]. This finding could be explained by the fact that β1 and γ1 proteins participate in multiple heterotrimers and therefore have broader functions than α1 chain that is restricted to two laminins.…”

“…Expression of lama1 is detected in the nervous and urogenital systems, pre-somitic mesoderm, some brain blood vessels and in the embryonic and mature lens ([12,13,15], and [22]). The important role of laminins/extracellular matrix/basement membranes in eye development and in an adult ocular function has been discussed in several reports [23-26] but the specific roles of different laminin subunits are only beginning to be elucidated.…”

Monoclonal anti-mouse laminin antibodies: AL-1 reacts with laminin α1 chain, AL-2 with laminin β1 chain, and AL-4 with the coiled-coil domain of laminin β1 chain

“…Genetic evidence and culture of embryonic stem cells have established that laminin-111 is an essential morphogen for the first fetal differentiation in mice, starting when endoderm-derived LM-111 induces embryonic stem cell conversion to polarized epiblast cells (Smyth et al, 1999;Li et al, 2001;Li et al, 2002;Miner et al, 2004, Schéele et al, 2005. The α1 chain has also been implicated in kidney stem cell conversion into epithelial cells (Klein et al, 1988), lung development (Schuger et al, 1997), and mammary epithelial cell polarization (Gudjonsson et al, 2002).…”