Gata1, a zinc-finger transcription factor, is essential for mammalian erythropoiesis. Erythroid cells that lack Gata1 apoptose, while Gata1 overexpression blocks differentiation. However, Gata1-overexpressing erythroid cells differentiate normally in vivo when wild-type cells are present,indicating that these cells produce a red cell differentiation signal (REDS)that rescues the defect in Gata1-overexpressing cells. On p. 3183,Gutiérrez et al. report that REDS is produced by committed erythroid cells. The researchers combine a tissue-specific Cre/loxP system and X inactivation to produce mice in which half the erythroid cells overexpress Gata1 and half are Gata1 null. These embryos are anaemic and die by E14, supporting a homotypic signalling mechanism in which mature erythroid cells produce REDS. Importantly, these results indicate that terminal differentiation during erythropoiesis (and presumably during other differentiation programmes) is not achieved by simply turning off self-renewal signals, but also requires specific differentiation signals.
Signalling RED for terminal differentiation
Signalling RED for terminal differentiation. Development 1 July 2004; 131 (13): e1303. doi:
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