Anteroposterior and dorsoventral patterning are coordinated by an identical patterning clock

Establishment of the body plan in vertebrates depends on the temporally coordinated patterning of tissues along the body axes. We have previously shown that dorsoventral (DV) tissues are temporally patterned progressively from anterior to posterior by a BMP signaling pathway. Here we report that DV patterning along the zebrafish anteroposterior (AP) axis is temporally coordinated with AP patterning by an identical patterning clock. We altered AP patterning by inhibiting or activating FGF, Wnt or retinoic acid signaling combined with inhibition of BMP signaling at a series of developmental time points, which revealed that the temporal progression of DV patterning is directly coordinated with AP patterning. We investigated how these signaling pathways are integrated and suggest a model for how DV and AP patterning are temporally coordinated. It has been shown that in Xenopus dorsal tissues FGF and Wnt signaling quell BMP signaling by degrading phosphorylated (P) Smad1/5, the BMP pathway signal transducer, via phosphorylation of the Smad1/5 linker region. We show that in zebrafish FGF/MAPK, but not Wnt/GSK3, phosphorylation of the Smad1/5 linker region localizes to a ventral vegetal gastrula region that could coordinate DV patterning with AP patterning ventrally without degrading P-Smad1/5. Furthermore, we demonstrate that alteration of the MAPK phosphorylation sites in the Smad5 linker causes precocious patterning of DV tissues along the AP axis during gastrulation. Thus, DV and AP patterning are intimately coordinated to allow cells to acquire both positional and temporal information simultaneously.