Ikaros in hemopoietic lineage determination and homeostasis

Studies on the molecular mechanisms that control hemopoietic differentiation have focused on signaling cascades and nuclear effectors that drive this complex developmental system in a regulated fashion. Here we review the role of Ikaros, the founding member of a unique family of zinc finger transcription factors in this developmental process. Studies on an Ikaros null mutation have revealed an essential role for this factor in lymphoid cell fate determination and at subsequent branch points of the T cell differentiation pathway. Differences in the phenotypes of a null and a dominant negative (DN) Ikaros mutation provide insight into a regulatory network through which Ikaros proteins exert their effects in development. In addition a comparative analysis of the hemopoietic stem cell and precursor compartment resulting from the two Ikaros mutations reveals a profound yet not absolute requirement for Ikaros in the production and differentiation of these populations.