CORRESPONDENCE

Notch signaling is a highly evolutionarily con-served pathway implicated in diverse functions including stem cell maintenance, cell fate spec-ification, cell proliferation, and apoptosis. When membrane-bound Notch receptors recognize ligands of the Delta and Jagged families, they are cleaved by metalloproteases and the -secretase complex, allowing the release of the intracellu-lar domain into the nucleus where it associates with cofactors to control a significant number of targets including the Hes family of genes (Artavanis-Tsakonas et al., 1999; Ilagan and Kopan, 2007). In the hematopoietic system, Notch is essential for the emergence of defini-tive hematopoietic stem cells (HSCs) during fetal life (Robert-Moreno et al., 2008) and in-dispensible for the commitment of progenitors to the T cell lineage (Zúñiga-Pflücker, 2004). Moreover, Notch1 appears to be the central oncogenic trigger in T cell acute lymphoblastic leukemia (T-ALL) in both humans and mice (Weng et al., 2004). Indeed, Notch1 (or its reg-ulator Fbw7) is commonly mutated, leading to constitutive activation of the Notch pathway in the majority of T-ALL patients (Malyukova et al., 2007; Maser et al., 2007; Thompson et al., 2007). In contrast to the T cell lineage where the role of Notch signaling is well defined, there is conflicting information on the role of Notch signaling in the function of adult stem cells (HSCs) and multipotential progen-itors and in the myeloerythroid compartmen