Differentiation and integrity of cardiac muscle cells are impaired in the absence of β1 integrin

Reinhard Fässler, Jürgen Rohwedel, Victor Maltsev, Wilhelm Bloch, Silvia Lentini, Kaomei Guan, Donald Gullberg, Jürgen Hescheler, Klaus Addicks, Anna M. Wobus*

*Corresponding author for this work
137 Citations (Scopus)

Abstract

Cellular interactions with substrata of the microenvironment are one of the major mechanisms for differentiation and morphogenesis. Many of these interactions are mediated via the β1 integrin subfamily of cell surface receptors, which are believed to transduce signals upon cell adhesion. We have used β1 integrin-deficient embryonic stem cells to test their ability to differentiate into cardiac muscle cells. We show here by several approaches that β1 integrin is important for normal cardiogenesis. First, the in vitro differentiation of β1 integrin-deficient embryonic stem cells into cardiac muscle cells is retarded. This is demonstrated by the delayed expression of cardiac muscle-specific genes and action potentials. Second, the specification of cardiac precursor cells into pacemaker-, atrial- and ventricular-like cells is significantly impaired in β1 integrin-deficient cells. The occurrence of atrial- and ventricular-like cells is reduced and transient. Only cells exhibiting pacemaker-like action potentials of high frequency and arrhythmias survive. Third, the sarcomeric architecture is incomplete and disarranged in the absence of β1 integrin. Fourth, β1-deficient embryonic stem cells can contribute to the developing heart in chimaeric mice but many areas with β1-null cells contain cell debris. The number of β1-null cells decreases from prenatal to postnatal stages and is lost completely in 6-month-old hearts. Thus, we conclude that interactions with the extracellular matrix via β1 integrin is necessary for differentiation and the maintenance of a specialized phenotype of cardiac muscle cells.

Original languageEnglish
JournalJournal of Cell Science
Volume109
Issue number13
Pages (from-to)2989-2999
Number of pages11
ISSN0021-9533
Publication statusPublished - 01.12.1996

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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