Among the three embryonic germ layers, the mesoderm plays a central role in the establishment of the vertebrate body plan. The mesoderm is specified by secreted signaling proteins from the FGF, Nodal, BMP and Wnt families. No new classes of extracellular mesoderm-inducing factors have been identified in more than two decades. Here, we show that the pinhead (pnhd) gene encodes a secreted protein that is essential for the activation of a subset of mesodermal markers in the Xenopus embryo. RNA sequencing revealed that many transcriptional targets of Pnhd are shared with those of the FGF pathway. Pnhd activity was accompanied by Erk phosphorylation and required FGF and Nodal but not Wnt signaling. We propose that during gastrulation Pnhd acts in the marginal zone to contribute to mesoderm heterogeneity via an FGF receptor-dependent positive feedback mechanism.

Author contributions

Conceptualization: O.O., S.Y.S.; Methodology: O.O., K.I., A.R., J.E., S.Y.S.; Software: S.Y.S.; Validation: O.O., K.I., J.E.; Formal analysis: O.O., A.R., S.Y.S.; Investigation: O.O., K.I., J.E., S.Y.S.; Data curation: O.O., K.I., A.R., S.Y.S.; Writing - original draft: O.O., S.Y.S.; Writing - review & editing: O.O., K.I., A.R., J.E.; Visualization: O.O.; Supervision: S.Y.S.; Project administration: S.Y.S.; Funding acquisition: S.Y.S.

Funding

This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (National Institutes of Health) (HD092990 to S.Y.S.). Deposited in PMC for release after 12 months.

Data availability

The RNA-seq data reported in this paper have been deposited in GEO under accession number GSE143795.

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