Ablation of Dido3 compromises lineage commitment of stem cells in vitro and during early embryonic development

A. Fütterer, Á Raya, M. Llorente, J. C. Izpisúa-Belmonte, J. L. De La Pompa, P. Klatt, C. Martínez-A*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


The death inducer obliterator (Dido) locus encodes three protein isoforms, of which Dido3 is the largest and most broadly expressed. Dido3 is a nuclear protein that forms part of the spindle assembly checkpoint (SAC) and is necessary for correct chromosome segregation in somatic and germ cells. Here we report that specific ablation of Dido3 function in mice causes lethal developmental defects at the onset of gastrulation. Although these defects are associated with centrosome amplification, spindle malformation and a DNA damage response, we provide evidence that embryonic lethality of the Dido3 mutation cannot be explained by its impact on chromosome segregation alone. We show that loss of Dido3 expression compromises differentiation of embryonic stem cells in vitro and of epiblast cells in vivo, resulting in early embryonic death at around day 8.5 of gestation. Close analysis of Dido3 mutant embryoid bodies indicates that ablation of Dido3, rather than producing a generalized differentiation blockade, delays the onset of lineage commitment at the primitive endoderm specification stage. The dual role of Dido3 in chromosome segregation and stem cell differentiation supports the implication of SAC components in stem cell fate decisions.

Original languageEnglish (US)
Pages (from-to)132-143
Number of pages12
JournalCell Death and Differentiation
Issue number1
StatePublished - Jan 2012
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements. We thank Drs K van Wely, V Trachana and C Pacios-Bras for critical discussion, L Almonacid of the DIO Genomics Group for low-density array analysis, L Kremer for anti-Dido antibody, the CNB Animal Facility for mouse handling and C Mark for editorial assistance. This work was supported in part by grants from the Spanish Ministry of Science and Innovation (SAF2010-21205 and PIB2010BZ-00564), the Madrid regional government (CAM S-BIO-0189-2006) and the EU (LSHB.CT-2005-518167). The Department of Immunology and Oncology was founded and is supported by the Spanish National Research Council (CSIC) and by Pfizer.


  • Dido3
  • apoptosis
  • embryogenesis
  • stem cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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