Although Wang et al. suggested that the mechanism of human tooth agenesis caused by MSX1 mutations may be independent of any synergism with PAX9. 45 Jia, S. et al.46 reported a novel mechanism BMP4-MSX1 pathway and OSR2 (protein odd-skipped-related) being implicated in tooth development by antagonistic regulation of secreted molecules involved in the WNT signaling pathway. Here, BMP4 is linked to tooth agenesis.