Fig. 9. The role of Elf5 in the TS cell lineage and the effects of its absence on embryonic development. (A) Model for the specification and maintenance of the TS lineage during early development. The effect of loss of function of the transcription factors Cdx2, Eomes and Elf5 is indicated (see text for discussion; TE, trophectoderm). (B,C) Model depicting the effect of the absence of ExE on embryonic development. (B) In wild-type pregastrula embryos, Furin and Spc4 protein produced by the ExE (green) diffuses (orange arrow) into the epiblast (blue), causing proteolytic activation of precursor Nodal (preNodal), which at these stages is produced from the intronic enhancer (InE) (Brennan et al., 2001; Norris et al., 2002). Activated Nodal protein positively acts (curved arrows) on its own transcription, as well as inducing the formation of the AVE (red). The lack of Elf5-dependent TS cell renewal in Elf5^-/- mutants leads to the absence of ExE at E5.5. The EPC, now adjacent to the epiblast, produces Spc4, which is sufficient to activate preNodal in the epiblast, thereby leading to correct AVE formation in Elf5 null mutants. (C) By E6.0 to 6.5, when gastrulation commences, Nodal transcription has come under the control of the Nodal-independent PEE enhancer (Norris et al., 2002; Vincent et al., 2003). In Elf5 mutants, the absence of the ExE results in the loss of the factor(s) required for Nodal transcription from the PEE enhancer. Candidates for such factors are Bmps (dashed red arrow; see text). The loss of Nodal transcription in Elf5^-/- embryos results in the absence of posterior gene expression and thus mesoderm (purple) is not formed.