Long-term, multilineage hematopoiesis occurs in the combined absence of β-catenin and γ-catenin

The canonical Writ signaling pathway plays key roles in stem-cell maintenance, progenitor cell expansion, and lineage decisions. Transcriptional responses induced by Writ depend on the association of either P-catenin or gamma-catenin with lymphoid enhancer factor/T cell factor transcription factors. Here we show that hematopoiesis, including thymopoiesis, is normal in the combined absence of beta- and gamma-catenin. Double-deficient hematopoietic stem cells maintain long-term re-population capacity and multilineage differentiation potential. Unexpectedly, 2 independent ex vivo reporter gene assays show that Writ signal transmission is maintained in double-deficient hematopoietic stem cells, thymocytes, or peripheral T cells. In contrast, Writ signaling is strongly reduced in thymocytes lacking TCF-1 or in nonhematopoietic cells devoid of P-catenin. These data provide the first evidence that hematopoletic cells can transduce canonical Writ signals in the combined absence of beta- and gamma-catenin.