Laminin alpha1 domains LG4-5 are essential for the complete differentiation of visceral endoderm.
The heterotrimeric basement membrane protein laminin-111 is essential for early mouse embryogenesis. Its beta1 and gamma1 chains are crucial for endoderm differentiation and for the formation of basement membranes, whereas alpha1 chain null mice only lack the extraembryonic Reichert's membrane. Nevertheless, mice deficient in the cell-binding alpha1 globular domains 4-5 (LG4-5) have a more severe phenotype than animals devoid of the whole alpha1 chain, as these domains are required for the formation of a polarized ectoderm. However, the influence of the alpha1LG4-5 domains on endoderm differentiation is unclear. We have used microarray analysis to compare the expression profiles of normal and alpha1LG4-5-deficient embryoid bodies and show that genes encoding secreted plasma proteins and proteins involved in endocytosis are reduced in alpha1LG4-5-deficient embryoid bodies, indicating incomplete differentiation of the visceral endoderm. Moreover, mice lacking alpha1LG4-5 display endoderm disorganization and a defective expression of the endoderm marker Dab2. We hypothesize that alpha1LG4-5 domains provide an autocrine signal necessary for the complete differentiation of a functional visceral endoderm and vital signals for the polarization of the epiblast.
Akerlund
Mikael
M
Department of Experimental Medical Science, Lund University, BMC B12, 221 84, Lund, Sweden. mikael.akerlund@med.lu.se
Carmignac
Virginie
V
Schéele
Susanne
S
Durbeej
Madeleine
M
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D004707:Endoderm / Q000166:cytology / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D007797:Laminin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051017:Apoptosis Regulatory Proteins; C478773:Dab2 protein, mouse; D007797:Laminin; C084098:laminin A