The ikaros gene encodes a family of early hematopoietic-and lymphocyte-restricted transcription factors. Mice homorygous for a germline mutation in the lkaros DNA-binding domain lack not only T and B lymphocytes and natural killer cells but also their earliest defined progenitors. In contrast, the erythroid and myeloid lineages were intact in these mutant mice. We propose that ikaros promotes differentiation of pluripotential hematopoietic stem ceil (s) into the lymphocyte pathways. In the absence of a functional lkaros gene, these stem cells are exclusively diverted into the erythroid and myeloid lineages. introduction

Development of the lymphoid system from pluripotent hematopoietic stem cells (HSCs) is a poorly characterized process. The existence and ontogeny of common or distinct lymphocyte progenitors for T, B, and natural killer (NK) ceil lineages and the sites of their production remain to be determined (Ikuta et al., 1992; Spangrude, 1989). In addition, thesignals that triggerand sustain thedifferentiation of progenitors to mature immunocompetent lymphocytes remain elusive. In many developmental systems, temporally expressed or activated transcription factors have been described that mediate ceil fate decisions and promote differentiation (reviewed by Skeath et al., 1992; Weintraub, 1993). These factors also may play a pivotal role at subsequent branch points of differentiation. Such developmental master switches may also exist for the lymphopoietic system.