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PINCH1 regulates cell-matrix and cell-cell adhesions, cell polarity and cell survival during the peri-implantation stage

Authors :
Shaohua Li
Attila Braun
Fabio Stanchi
Ulla M. Wewer
Oliver Kudlacek
Randi Bordoy
Peter D. Yurchenco
Reinhard Fässler
Markus Moser
Source :
Journal of cell science. 118(Pt 13)
Publication Year :
2005

Abstract

PINCH1 is composed of 5 LIM domains, binds integrin-linked kinase (ILK) and locates to integrin-mediated adhesion sites. In order to investigate PINCH1 function we generated mice and embryonic stem (ES) cell-derived embryoid bodies (EBs) lacking the PINCH1 gene. Similar to mice lacking β1 integrin or Ilk, loss of PINCH1 arrested development at the peri-implantation stage. In contrast to β1 integrin or Ilk mutants, however, disruption of the PINCH1 gene produced implantation chambers with visible cell clumps even at embryonic day 9.5. In order to define the phenotype leading to the peri-implantation lethality we made PINCH1-null EBs and found similar but also additional defects not observed in β1 integrin or Ilk mutant EBs. The similarities included abnormal epiblast polarity, impaired cavitation and detachment of endoderm and epiblast from basement membranes. Additional defects, which were not observed in β1 integrin- or ILK-deficient mice or EBs, included abnormal cell-cell adhesion of endoderm and epiblast as well as the presence of apoptotic cells in the endodermal cell layer. Although ILK and PINCH1 were shown to be involved in the phosphorylation of serine-473 of PKB/Akt, immunostaining with specific antibodies revealed no apparent alteration of PKB/Akt phosphorylation in PINCH1-deficient EBs. Altogether these data demonstrate an important role of PINCH1 for integrin function, actin organization, cell-cell adhesion and endodermal cell survival during the implanting of mouse embryos.

Details

ISSN :
00219533
Volume :
118
Issue :
Pt 13
Database :
OpenAIRE
Journal :
Journal of cell science
Accession number :
edsair.doi.dedup.....c6b136b6a0fb6dd18de9a6e354355274