Overlapping and independent functions of fibronectin receptor integrins in early mesodermal development

Joy T. Yang, Bernhard L. Bader, Jordan A. Kreidberg, Mollie Ullman-Culleré, Jane E. Trevithick, Richard O. Hynes

Research output: Contribution to journalArticle

Abstract

Mouse embryos deficient in fibronectin (FN-null) die at E8.5 with mesodermal defects. Eight integrin heterodimers α3β1, α4β1, α5β1, α8β1, avβ1, αvβ3, αvβ6, and αIIbβ3 can bind to FN. However, embryos deficient in each of these integrins exhibit less severe defects than do FN- null embryos, raising questions as to which integrin(s) are the key FN receptors for these early FN-dependent processes, α5β1 is believed to be the key receptor and α5-null embryos display mesodermal defects similar to, although less severe than, those of FN-null. Here we report that the α5-null mutation exhibits a more severe phenotype on a 129Sv (129) than on a C57BL/6 (B6) background, as does the FN-null mutation. While α5-null/B6 embryos develop normal headfolds, α5-null/129 embryos have headfold defects similar to those of FN-null. The differences between FN-null and α5-null embryos, however, cannot be attributed to genetic background. FN-null embryos never form somites, whereas in α5-null/129 embryos the somites do condense but fail to epithelialize. Second, we examined double mutants carrying all possible pairwise combinations of null mutations in α3, α4, and α5 integrin genes. There was no evidence for any synergy between paired mutations, suggesting that these integrin genes do not have overlapping functions during early embryonic development. Finally, we examined double- mutant embryos deficient in both α5 and αv integrin genes. These double- mutant embryos have an amniotic defect similar to that of FN-null embryos, but die even earlier with a defect in gastrulation. These studies thus revealed a gradation in the severity of defects in the mutations α5(-/-); αv(-/-) > FN(-/-) (129) > FN(-/-) (B6) > α5(-/-) (129) > α5(-/-) (B6), and in each step in this series there is a certain degree of phenotypic overlap, suggesting that the defects arising from these mutations may result from disruptions of the same embryonic process.

Original languageEnglish (US)
Pages (from-to)264-277
Number of pages14
JournalDevelopmental Biology
Volume215
Issue number2
DOIs
Publication statusPublished - Nov 15 1999
Externally publishedYes

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Keywords

  • Fibronectin
  • Gastrulation
  • Integrins
  • Somitogenesis

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Yang, J. T., Bader, B. L., Kreidberg, J. A., Ullman-Culleré, M., Trevithick, J. E., & Hynes, R. O. (1999). Overlapping and independent functions of fibronectin receptor integrins in early mesodermal development. Developmental Biology, 215(2), 264-277. https://doi.org/10.1006/dbio.1999.9451