TBX6 is a T-box transcription factor that functions as a master regulator of paraxial mesoderm specification during embryonic development 1. It plays a critical role in determining cell fate decisions between neural and mesodermal lineages by suppressing neural development through downregulation of SOX2 enhancers 2. During somitogenesis, TBX6 acts as a key segmentation clock component regulating vertebral formation 3. Genetically, TBX6 operates through compound inheritance mechanisms in congenital vertebral malformations (CVMs). Heterozygous null mutations and common hypomorphic alleles together account for approximately 11% of congenital scoliosis cases 4. Conversely, increased TBX6 dosage from 16p11.2 duplications also causes CVMs, particularly affecting cervical vertebrae, with 60% of mice with elevated Tbx6 expression manifesting spinal defects 5. These dosage-sensitive effects highlight the importance of precise TBX6 expression levels. Beyond skeletal development, TBX6 participates in myogenic differentiation and cardiac pathophysiology. During skeletal muscle organoid development, TBX6-positive paraxial mesodermal progenitors constitute the primary myogenic lineage 6. In cardiac tissue, the Dot1L-mediated histone modification axis promotes Tbx6 expression, which drives stress-induced cardiac hypertrophy 7. TBX6 variants have also been associated with Mayer-Rokitansky-Küster-Hauser syndrome through 16p11.2 deletions 8.