Roles for laminin in embryogenesis: Exencephaly, syndactyly, and placentopathy in mice lacking the laminin α5 chain

Jeffrey H. Miner, Jeanette Cunningham, Joshua R. Sanes

Research output: Contribution to journalArticlepeer-review

372 Scopus citations

Abstract

Laminins are the major noncollagenous glycoproteins of all basal laminae (BLs). They are α/β/γ 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 α5 chain is required during embryogenesis. The α5 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 α5 retain or acquire other α chains. Embryos lacking laminin α5 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 α5 positive in controls and that appear ultrastructurally abnormal in its absence. Other laminin α 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.

Original languageEnglish
Pages (from-to)1713-1723
Number of pages11
JournalJournal of Cell Biology
Volume143
Issue number6
DOIs
StatePublished - Dec 14 1998

Keywords

  • Basement membrane
  • Development
  • Knockout mice
  • Limb deformities
  • Placenta

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