Contingent gene regulatory networks and B cell fate specification

The B cell developmental pathway represents a leading system for the analysis of regulatory circuits that orchestrate cell fate specification and commitment. Considerable progress has been achieved within the past decade in the identification and genetic analysis of various regulatory components. These components include the transcription factors PU.1, Ikaros, Bcl11a, E2A, EBF, and Pax-5, as well as the cytokine receptors Flk2 and IL-7R. Experimental evidence of connectivity among the regulatory components is used to assemble sequentially acting and contingent gene regulatory networks. Transient signaling inputs, self-sustaining positive feedback loops, and cross-antagonism among alternate cell fate determinants are key features of the proposed networks that instruct the development of B lymphocyte precursors from hematopoietic stem cells.