Throughout development, signalling pathways and transcription factor networks control the differentiation of stem cells and progenitor cells but how their effects are integrated is poorly understood. Now, on p. 2071, Lohmann and Bieker reveal how Bmp4 signalling and Gata transcription factors interact to control haematopoiesis in mice by studying the regulation of the erythroid-specific transcription factor Eklf during this process. In differentiating embryonic stem (ES) cells, they report, Eklf expression is initiated in haematopoietic progenitor cells before erythroid commitment. Using a new RNAi-based loss-of-function approach in embryoid bodies, among other approaches, they show that Gata2 and Smad5 (a downstream effector of Bmp4 signalling) cooperate to induce Eklf expression in erythroid-megakaryocytic progenitor cells. The maintenance of Eklf expression in committed erythroid cells, however, is regulated by Gata1 in a Smad-independent manner. These results suggest that Eklf is poised to regulate lineage fate decisions during early haematopoiesis and, more generally, show how the factors that govern early mouse development can be studied in ES cells undergoing in vitro differentiation.
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