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Normal Hemopoiesis and Lymphopoiesis in the Combined Absence of Numb and Numblike¹

Anne Wilson^*, Denis-Luc Ardiet^2,, Catherine Saner^2,, Nathalie Vilain, Friedrich Beermann, Michel Aguet^,, H. Robson MacDonald^3,* and Olav Zilian^3,4,

^* Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne; Swiss Institute for Experimental Cancer Research, Epalinges, Switzerland; and School of Life Sciences, Ecole Polytechnique Fedérale de Lausanne, Lausanne, Switzerland

The mammalian ortholog of the conserved Drosophila adaptor protein Numb (Nb) and its homolog Numblike (Nbl) modulate neuronal cell fate determination at least in part by antagonizing Notch signaling. Because the Notch pathway has been implicated in regulating hemopoietic stem cell self-renewal and T cell fate specification in mammals, we investigated the role of Nb and Nbl in hemopoiesis using conditional gene targeting. Surprisingly simultaneous deletion of both Nb and Nbl in murine bone marrow precursors did not affect the ability of stem cells to self-renew or to give rise to differentiated myeloid or lymphoid progeny, even under competitive conditions in mixed chimeras. Furthermore, T cell fate specification and intrathymic T cell development were unaffected in the combined absence of Nb and Nbl. Collectively our data indicate that the Nb family of adaptor proteins is dispensable for hemopoiesis and lymphopoiesis in mice, despite their proposed role in neuronal stem cell development.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by the Swiss National Science Foundation (to M.A.) and by Grant SKL 1125-02-2001 from the Swiss Cancer League (to O.Z.).

² D.-L.A. and C.S. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. H. Robson MacDonald, Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, CH-1066 Epalinges, Switzerland. E-mail address: HughRobson.MacDonald{at}isrec.ch or Olav Zilian, Helvea SA, CH-1207, Geneva, Switzerland. E-mail address: ozilian{at}helvea.com

⁴ Current address: Helvea SA, Rue de Jargonnant 5, 1207 Geneva, Switzerland.

⁵ Abbreviations used in this paper: Nb, Numb; Nbl, Numblike; BM, bone marrow; dKO, double knockout; DN, double negative; Lin^–, lineage-negative; LSK, Lin^–Sca1⁺c-kit⁺; CMP, common myeloid precursor; CLP, common lymphoid precursor; HSC, hemopoietic stem cell; pIpC, polyinosinic-polycytidylic.

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