Temporal regulation of epithelium formation

Abstract/SummaryTo establish the animal body plan, embryos link the external epidermis to the internal digestive tract. In Caenorhabditis elegans, this linkage is achieved by the Arcade Cells, which form an epithelial bridge between the foregut and epidermis, but little is known about how development of these three epithelia is coordinated temporally. The Arcade Cell epithelium is generated after the epidermis and digestive tract epithelia have matured, ensuring that both organs can withstand the mechanical stress of embryo elongation; mis-timing of epithelium formation leads to defects in morphogenesis. Here, we report that temporal regulation of the Arcade Cell epithelium is mediated by the pioneer transcription factor PHA-4/FoxA, the cytoskeletal regulator ZEN-4/MKLP and the polarity protein PAR-6. We find that PHA-4 activates expression of a broad cohort of epithelial genes. However, accumulation of protein is delayed by ZEN-4, acting in concert with its partner CYK-4/MgcRacGAP. Finally, PAR-6 localizes factors within adherens junctions and at the apical surface, leading to Arcade Cell polarity. The results reveal that the timing of a landmark event during embryonic morphogenesis is mediated by the concerted action of four proteins that delay the formation of an epithelial bridge. In addition, we find that FoxA associates with many epithelial genes in mammals, suggesting that regulation of epithelial identity may be a conserved feature of FoxA factors and a contributor to FoxA function in development and cancer.