Simultaneous loss of β- and γ-catenin does not perturb hematopoiesis or lymphopoiesis

• Published in: Blood 2008-01, Vol.111 (1), p.160-164
• Main Authors: Koch, Ute, Wilson, Anne, Cobas, Monica, Kemler, Rolf, MacDonald, H. Robson, Radtke, Freddy
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - cytology; beta Catenin - genetics; beta Catenin - metabolism; Biological and medical sciences; Bone Marrow Transplantation; Chimera; Female; gamma Catenin - genetics; gamma Catenin - metabolism; Hematologic and hematopoietic diseases; Hematopoiesis - physiology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Lymphopoiesis - physiology; Male; Medical sciences; Mice; Mice, Mutant Strains; Pregnancy; T-Lymphocytes - cytology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-07-099754

Hematopietic stem cells (HSCs) maintain life-long hematopoiesis in the bone marrow via their ability to self-renew and to differentiate into all blood lineages. Although a central role for the canonical wnt signaling pathway has been suggested in HSC self-renewal as well as in the development of B and T cells, conditional deletion of β-catenin (which is considered to be essential for Wnt signaling) has no effect on hematopoiesis or lymphopoiesis. Here, we address whether this discrepancy can be explained by a redundant and compensatory function of γ-catenin, a close homolog of β-catenin. Unexpectedly, we find that combined deficiency of β- and γ-catenin in hematopoietic progenitors does not impair their ability to self-renew and to reconstitute all myeloid, erythroid, and lymphoid lineages, even in competitive mixed chimeras and serial transplantations. These results exclude an essential role for canonical Wnt signaling (as mediated by β- and/or γ-catenin) during hematopoiesis and lymphopoiesis.