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© The Rockefeller University Press, 0021-9525/1998//1713 $5.00
The Journal of Cell Biology, Volume 143, Number 6, , 1998 1713-1723


Article

Roles for Laminin in Embryogenesis: Exencephaly, Syndactyly, and Placentopathy in Mice Lacking the Laminin {alpha}5 Chain



Jeffrey H. Miner*, Jeanette Cunningham{ddagger}, and Joshua R. Sanes{ddagger}

* Department of Medicine, Renal Division and {ddagger} Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110

Laminins are the major noncollagenous glycoproteins of all basal laminae (BLs). They are {alpha}/β/{gamma} heterotrimers assembled from 10 known chains, and they subserve both structural and signaling roles. Previously described mutations in laminin chain genes result in diverse disorders that are manifested postnatally and therefore provide little insight into laminin's roles in embryonic development. Here, we show that the laminin {alpha}5 chain is required during embryogenesis. The {alpha}5 chain is present in virtually all BLs of early somite stage embryos and then becomes restricted to specific BLs as development proceeds, including those of the surface ectoderm and placental vasculature. BLs that lose {alpha}5 retain or acquire other {alpha} chains. Embryos lacking laminin {alpha}5 die late in embryogenesis. They exhibit multiple developmental defects, including failure of anterior neural tube closure (exencephaly), failure of digit septation (syndactyly), and dysmorphogenesis of the placental labyrinth. These defects are all attributable to defects in BLs that are {alpha}5 positive in controls and that appear ultrastructurally abnormal in its absence. Other laminin {alpha} chains accumulate in these BLs, but this compensation is apparently functionally inadequate. Our results identify new roles for laminins and BLs in diverse developmental processes.

Key Words: basement membrane • development • placenta • knockout mice • limb deformities



Abbreviations used in this paper: AER, apical ectodermal ridge; BL, basal lamina; BrdU, 5-bromo-2'-deoxy-uridine; E, embryonic day.



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