The conserved role and divergent regulation of foxa, a pan-eumetazoan developmental regulatory gene: Experimental and historical aspects of evolutionary bioscience

Foxa is a forkhead transcription factor that is expressed in the endoderm lineage across metazoans. Orthologs of foxa are expressed in cells that intercalate, polarize, and form tight junctions in the digestive tracts of the mouse, the sea urchin, and the nematode and in the chordate notochord. The loss of foxa expression eliminates these morphogenetic processes. The remarkable similarity in foxa phenotypes in these diverse organisms raises the following questions: why is the developmental role of Foxa so highly conserved? Is foxa transcriptional regulation as conserved as its developmental role? Comparison of the regulation of foxa orthologs in sea urchin and in Caenorhabditis elegans shows that foxa transcriptional regulation has diverged significantly between these two organisms, particularly in the cells that contribute to the C. elegans pharynx formation. We suggest that the similarity of foxa phenotype is due to its role in an ancestral gene regulatory network that controlled intercalation followed by mesenchymal-to-epithelial transition. foxa transcriptional regulation had evolved to support the developmental program in each species so foxa would play its role controlling morphogenesis at the necessary embryonic address.