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Over the past decade, recognition of the profound impact of the TBX4 (T-box 4) gene, which encodes a member of the evolutionarily conserved family of T-box–containing transcription factors, on respiratory diseases has emerged. The developmental importance of TBX4 is emphasized by the association of TBX4 variants with congenital disorders involving respiratory and skeletal structures; however, the exact role of TBX4 in human development remains incompletely understood. This study discusses the developmental, tissue-specific, and pathological TBX4 functions identified through human and animal studies and reviews the published TBX4 variants resulting in variable disease phenotypes. The study outlines future research directions to fill the gaps in our understanding of TBX4 function and how TBX4 disruption affects development.
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