Bone morphogenetic proteins (Bmps), which regulate cell-cell signalling in animal development, are controlled by a network of secreted proteins including Twisted gastrulation (Tsg). Tsg can inhibit or promote Bmp signalling,depending on the developmental system. On p. 413, Zakin and De Robertis investigate Tsg regulation of Bmp4 signalling during mouse development. The researchers describe how targeted inactivation of the Tsg gene alone results in undersized mice with mild vertebral defects. Similarly, previous studies have indicated that Bmp+/- mice have only mild defects. By contrast, the Tsg-/-, Bmp4+/- compound mutants derived by Zakin and De Robertis die at birth and have major brain abnormalities, including holoprosencephaly, a disorder in which the embryonic forebrain fails to divide into two lobes. These results indicate that Tsg acts to promote Bmp4 signalling during forebrain development.