Signalling through transforming growth factor β (Tgfβ)superfamily members is important throughout vertebrate development, and Smad4 is generally regarded as a key intracellular effector of all Tgfβ-related signals. Surprisingly, Chu and colleagues now report that Smad4 is required for only a subset of Tgfβ-related signals during early mouse development(see p. 3501). By using a Smad4 conditional allele to inactive the Smad4 gene in the early epiblast, they show that the primary anteroposterior axis is established and gastrulation initiated in the absence of Smad4. Similarly,many bone morphogenetic protein (Bmp) and Tgfβ-regulated processes involved in mesoderm formation and patterning are relatively unaffected. However, anterior primitive streak derivatives fail to form. The researchers conclude that Smad4 is essential for the Nodal signalling pathway that specifies the anterior primitive streak, but is dispensable for the transduction of some Bmp signals during early development.

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