Runx-dependent expression of PKC is critical for cell survival in the sea urchin embryo

Carrie Dickey-Sims, Anthony J. Robertson, Dawn E. Rupp, John J. McCarthy, James A. Coffman

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Background: Runx transcription factors play critical roles in the developmental control of cell fate and contribute variously as oncoproteins and tumor suppressors to leukemia and other cancers. To discover fundamental Runx functions in the cell biology of animal development, we have employed morpholino antisense-mediated knockdown of the sea urchin Runx protein SpRunt-1. Previously we showed that embryos depleted of SpRunt-I arrest development at early gastrula stage and underexpress the conventional protein kinase C SpPKC1. Results: We report here that SpRunt-I deficiency leads to ectopic cell proliferation and extensive apoptosis. Suppression of the apoptosis by pharmacological inhibition of caspase-3 prevents the ectopic proliferation and rescues gastrulation, indicating that many of the overt defects obtained by knockdown of SpRunt-1 are secondary to the apoptosis. Inhibition or knockdown of SpPKCI also causes apoptosis, while cell survival is rescued in SpRunt-I morphant embryos coinjected with SpPKCI mRNA, suggesting that the apoptosis associated with SpRunt-I deficiency is caused by the deficit in SpPKCI expression. Chromatin immunoprecipitation indicates that SpRunt-I interacts physically with SpPKCI in vivo, and cis-regulatory analysis shows that this interaction activates SpPKCI transcription. Conclusions: Our results show that Runx-dependent activation of SpPKCI is essential for maintaining protein kinase C activity at levels conducive to cell survival during embryogenesis.

Original languageEnglish
Article number18
JournalBMC Biology
StatePublished - Aug 2 2005

ASJC Scopus subject areas

  • Biotechnology
  • Structural Biology
  • Ecology, Evolution, Behavior and Systematics
  • Physiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • Plant Science
  • Developmental Biology
  • Cell Biology


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