Hox transcription factors are essential regulators of embryonic patterning, and loss of HOXA13 function causes severe limb malformations in humans and mice. This study demonstrates that HOXA13 directly regulates bone morphogenetic protein (BMP) signaling during autopod development. HOXA13 binds and activates novel enhancer regions of Bmp2 and Bmp7 and represses Sostdc1, a BMP antagonist, thereby promoting proper BMP signaling. Reduced BMP activity contributes to the Hoxa13 mutant limb phenotype, which can be partially rescued by exogenous BMPs. These findings provide a mechanistic link between HOXA13, BMP signaling, and limb patterning.
