Multifaceted role of T-box transcription factor 4: From embryonic development to disease pathogenesis

T-box transcription factor 4 (TBX4), a crucial member of the T-box gene family, is essential for embryonic development, particularly in the formation of hindlimbs and lungs. Beyond these developmental roles, TBX4 is integral for maintaining the structural integrity and function of the respiratory, motor, and nervous systems. Dysregulation of TBX4 is implicated in serious diseases, including pulmonary hypertension, small patella syndrome, and tracheal stenosis, with mutations and aberrant expression patterns emerging as potential diagnostic markers. Additionally, TBX4 contributes to tumorigenesis in cancers such as pancreatic, lung, and bladder cancers, where recent studies suggest DNA methylation as a primary mechanism underlying TBX4 suppression, positioning it as a promising prognostic marker. Despite these advances, the precise functions and regulatory mechanisms of TBX4 remain insufficiently understood. This review consolidates current knowledge on the roles and molecular mechanisms of TBX4 in mammalian embryonic development and its association with diseases, highlighting the need for further research into its contributions to human health.