Two papers in this issue focus on the role of growth differentiation factor 3 (GDF3) in early embryonic development. Mammalian GDF3 - which belongs to the bone morphogenetic protein (BMP) branch of the TGFβ superfamily - shares considerable amino acid similarity with Xenopus Vg1. By studying the role of GDF3 in early mouse patterning, Chen et al. (see p. 319) have found that Vg1 activity is remarkably well conserved. In Xenopus, Vg1 is essential for early patterning and signals through a Nodal-like pathway (see Development 133, 15-20). Here, the authors report that Gdf3-null mouse mutants resemble mice with absent or reduced Nodal signalling. Moreover, they report that GDF3 can interact with Nodal co-receptors and antagonists. Nodal signalling is crucial for the formation and positioning of the anterior visceral endoderm (AVE), which patterns the anteroposterior axis of the embryo. The researchers found that ∼30% of Gdf3 null mutants have an abnormally formed or positioned AVE, and they conclude that, like Vg1, GDF3 is required for Nodal pathway activity and for proper axial patterning in the early embryo.

In an accompanying paper (see p. 209), GDF3 and Nodal are reported to have even earlier roles in development than hitherto realised. By exploring the role of GDF3 in embryonic stem (ES) cells, Levine and Brivanlou have found that while higher GDF3 expression maintains pluripotency in human ES cells, it is lower GDF3 expression that maintains pluripotency in mouse ES cells. This apparent contradiction is consistent with their finding that GDF3 directly inhibits BMP4. BMPs, which are necessary for cell fate decisions in the blastocyst, promote human ES cell differentiation but maintain mouse ES cells in an undifferentiated state. The authors discuss several potential mechanisms - such as different sensitivities to BMP signalling - for these species-specific responses.