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  • The EMBO Journal (2004) 23, 1834 - 1844
  • doi:10.1038/sj.emboj.7600188

Published online: 1 April 2004

SRF regulates Bcl-2 expression and promotes cell survival during murine embryonic development

Gerhard Schratt1,ac, Ulrike Philippar1,bc, Dirk Hockemeyer1, Heinz Schwarz2, Siegfried Alberti1 and Alfred Nordheim1

  1. Interfakultäres Institut für Zellbiologie, Abteilung Molekularbiologie, Universität Tübingen, Auf der Morgenstelle, Tübingen, Germany
  2. Max-Planck-Institut für Entwicklungsbiologie, Spemannstrasse, Tübingen, Germany

Correspondence to:

Alfred Nordheim, Interfakultäres Institut für Zellbiologie, Abteilung Molekularbiologie, Universität Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany. Tel.: +49 7071 297 8898; Fax: +49 7071 295 359; E-mail: alfred.nordheim@uni-tuebingen.de

aPresent address: Division of Neuroscience, Children's Hospital and Department of Neurobiology, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, USA

bPresent address: Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, USA

cThese two authors contributed equally to this work

Received 19 August 2003; Accepted 5 March 2004

The transcription factor serum response factor (SRF) controls the expression of genes involved in cellular proliferation and differentiation. Interestingly, SRF also promotes cell survival by regulating the expression of antiapoptotic genes. In in vitro differentiating murine embryonic stem (ES) cells, SRF deficiency leads to increased apoptosis. Loss of SRF correlates with impaired expression of the antiapoptotic Bcl-2 and Bcl-xl genes. SRF binds the Bcl-2 promoter in vivo and activates Bcl-2 transcription. Reconstituting Bcl-2 in Srf(-/-) ES cells rescues these cells from apoptosis, demonstrating that SRF-dependent Bcl-2 expression is critical for ES cell survival. At the multicellular level, SRF deficiency leads to impaired cavitation and reduced Bcl-2 expression in embryoid bodies (EBs) and inappropriate apoptosis in both EBs and pregastrulation mouse embryos. Thus, our data from genetic and cellular studies uncover SRF-regulated Bcl-2 expression as a novel mechanism that is important for cell survival during early murine embryogenesis.

  • Keywords:

    • apoptosis,
    • Bcl-2,
    • cavitation,
    • ES cells,
    • SRF