Abstract
The human esophagus, derived from the anterior foregut endoderm, requires proper dorsal-ventral patterning for development. The transcription factor SOX2, crucial in this process, when dysregulated, leads to congenital esophageal abnormalities. EPHA2, a receptor tyrosine kinase, is vital in various developmental processes and cancer models, where it activates SOX2. This study demonstrates that EPHA2 regulates SOX2 expression during esophageal development using human iPSCs and iPSC-derived human esophageal organoids (HEO). Inhibition of EPHA2 decreased iPSC-derived HEO formation and SOX2 expression. These findings provide evidence of EPHA2 as being a key regulator of SOX2 signaling in early esophageal development. HIGHLIGHTS: SOX2 is crucial for proper esophageal development.EPHA2 is a receptor tyrosine kinase involved in various developmental processes.EPHA2 activates SOX2.Inhibition of EPHA2 decreased SOX2 expression and human esophageal organoid formation.