The zebrafish forkhead transcription factor FoxH1/Fast1 is a modulator of Nodal signaling required for organizer formation

Background: Signaling molecules related to the Nodal protein play essential roles in the formation and patterning of the gastrula organizer and the ge rm layers during vertebrate development. The forkhead transcription factor FoxH1 (also known as Fast1) is a component of the Nodal signaling pathway. Although different roles have been suggested for FoxH1, its specific functi on during development is still unclear. Results: We report that the zebrafish locus schmalspur (sur) encodes a memb er of the FoxH1 family. Maternal sur transcripts were localized to the anim al pole during oogenesis, Further expression was detected in a dorsoventral gradient at the onset of gastrulation and in specific domains in the organ izer, notochord and lateral plate mesoderm. Embryos lacking zygotic sur fun ction had variable deficiencies of prechordal plate and ventral neuroectode rm. In the absence of both maternal and zygotic sur function, embryos faile d to form a morphologically distinct gastrula organizer and, later, develop ed severe defects in all axial structures. In these embryos, expression of nodal genes was initiated but not maintained. Unlike embryos lacking Nodal signaling, sur mutants formed endoderm and paraxial mesoderm. Conclusions: FoxH1 is involved in regulatory feedback loops that control th e duration and intensity of Nodal signals in early patterning. In zebrafish , FoxH1 is not essential to induce Nodal-dependent cell fates, but its func tion is central in modulating and enhancing morphogenetic Nodal signals.