A member of the forkhead class of transcription factors from sea urchins (Spfkh1) that is expressed specifically in the endoderm of developing embryos has been identified. Spfkh1 was expressed transiently in the embryo, with peak levels of messenger ribonucleic acid (mRNA) accumulating at the time endoderm invaginated into the interior of the embryo. Expression was limited to the invaginating endoderm in the early gastrula, then became further restricted to the base of the invaginating gut at the mid-gastrula stage. Expression diminished by the end of gastrulation. This expression pattern indicates that Spfkh1 mRNA accumulates in endodermal cells as they invaginate, but disappears rapidly in endodermal cells that undergo convergent extension. Treatment of embryos during cleavage stages with lithium or phorbol esters caused an increase in Spfkh1 mRNA accumulation and expanded the domain of expression of Spfkh1, suggesting that signaling through the inositol-tris-phosphate protein kinase C (IP3-PKC) signaling pathway is upstream of Spfkh1 expression. The expression pattern of Spfkh1 suggests that it is centrally involved in specification and/or differentiation of the gut. Disruption of the extracellular matrix (ECM) prevents formation of the gut, but does not inhibit initiation of Spfkh1 expression. Embryos arrested prior to gastrulation continued to express Spfkh1 well past the time it was down-regulated in normal embryos, suggesting the ECM or cell movement is required for the decrease in Spfkh1 mRNA during gastrulation.