During mammalian embryogenesis, substantial cell proliferation occurs before the establishment of the body plan during gastrulation. Thus, before gastrulation, individual embryonic cells must be pluripotent. In vitro experiments with embryonic stem cells (ESCs) have indicated that the transcription factors Oct4, Sox2 and Nanog are components of a gene regulatory network (GRN) that stimulates self-renewal of pluripotent cells and have identified Tcf7l1 (Tcf3) as an inhibitor of GRN activity. But what is Tcf7l1’s function during embryonic development? To find out, Bradley Merrill and colleagues have been examining embryogenesis in Tcf7l1-/- mouse embryos (see ). They report that mesoderm specification is delayed in these embryos, thereby uncoupling it from primitive streak induction. Moreover, in vitro, Tcf7l1 activity is necessary to switch the response of pluripotent ESCs to Wnt/β-catenin signalling from self-renewal to mesoderm specification. Thus, the researchers suggest, Tcf7l1 prepares pluripotent epiblast cells in gastrulating mouse embryos for lineage specification and ensures that lineage specification is coordinated with the dynamic cellular events that occur during gastrulation.
