Simultaneous loss of beta- and gamma-catenin does not perturb hematopoiesis or lymphopoiesis.
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 beta-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 gamma-catenin, a close homolog of beta-catenin. Unexpectedly, we find that combined deficiency of beta- and gamma-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 beta- and/or gamma-catenin) during hematopoiesis and lymphopoiesis.
Koch
Ute
U
Swiss Institute for Experimental Cancer Research (ISREC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Epalinges, Switzerland.
Wilson
Anne
A
Cobas
Monica
M
Kemler
Rolf
R
Macdonald
H Robson
HR
Radtke
Freddy
F
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D016026:Bone Marrow Transplantation; D002678:Chimera; D005260:Female; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D038041:Lymphopoiesis / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011247:Pregnancy; D013601:T-Lymphocytes / Q000166:cytology; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism; D051185:gamma Catenin / Q000235:genetics* / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D051176:beta Catenin; D051185:gamma Catenin