Underlying the developing vertebrate forebrain is the prechordal mesoderm, which secretes sonic hedgehog (Shh) at a precise developmental time. The tight temporal regulation of this morphogen is crucial for the specification of several ventral cell types in the forebrain. However, little is known about the signals that limit Shh expression temporally. Nodal is expressed in the prechordal mesoderm and had previously been suggested to interact with Shh during ventral forebrain development. Now, using the chick embryo, Marysia Placzek and colleagues (p. 3821) show that Shh expression in the prechordal mesoderm is regulated by proNodal, the precursor of Nodal. Surprisingly, proNodal maintains Shh expression by a non-canonical route: binding to and activating FGFR3. Through this route, proNodal antagonises BMP7 and pSmad1/5/8, which suppresses Shh expression. Together with previous findings, this study suggests that whereas Nodal operates through canonical signalling to induce prechordal mesoderm, it acts via a non-canonical route involving FGFR3 to control the expression of Shh in the prechordal mesoderm.
- © 2015. Published by The Company of Biologists Ltd