Beta-catenin is vital for the integrity of mouse embryonic stem cells.
β-Catenin mediated Wnt-signaling is assumed to play a major function in embryonic stem cells in maintaining their stem cell character and the exit from this unique trait. The complexity of β-catenin action and conflicting results on the role of β-catenin in maintaining the pluripotent state have made it difficult to understand its precise cellular and molecular functions. To attempt this issue we have generated new genetically modified mouse embryonic stem cell lines allowing for the deletion of β-catenin in a controlled manner by taking advantage of the Cre-ER-T2 system and analyzed the effects in a narrow time window shortly after ablation. By using this approach, rather then taking long term cultured β-catenin null cell lines we demonstrate that β-catenin is dispensable for the maintenance of pluripotency associated genes. In addition we observed that the removal of β-catenin leads to a strong increase of cell death, the appearance of multiple clustered functional centrosomes most likely due to a mis-regulation of the polo-like-kinase 2 and furthermore, alterations in chromosome segregation. Our study demonstrates the importance of β-catenin in maintaining correct cellular functions and helps to understand its role in embryonic stem cells.
Max-Planck Institute of Immunobiology and Epigenetics, Emeritus Laboratory, Freiburg, Germany.
Angelo
A
Raggioli
Max-Planck Institute of Immunobiology and Epigenetics, Emeritus Laboratory, Freiburg, Germany ; Institute of Embryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Basel, Switzerland.
Dirk
D
Junghans
Max-Planck Institute of Immunobiology and Epigenetics, Emeritus Laboratory, Freiburg, Germany.
Stefan
S
Rudloff
Max-Planck Institute of Immunobiology and Epigenetics, Emeritus Laboratory, Freiburg, Germany.
Rolf
R
Kemler
D000818:Animals; D016923:Cell Death; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000378:metabolism*; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism*
D051176:beta Catenin; D017346:Protein Serine-Threonine Kinases; C444640:serum-inducible kinase