Bmp signaling regulates a dosage dependent transcriptional program to control facial skeletal development.

Conditional Bmp4 overexpression (Bmp4 OE), using a tetracycline regulated Bmp4 gain of function allele, resulted in facial skeletal changes that were most dramatic after an E10.5 Bmp4 induction. We identified a number of genes predominantly transcriptional regulators controlling self-renewal, osteoblast differentiation, and negative Bmp autoregulation whose expression were change after Bmp4 overexpression in the cranial neural crest cells. We performed expression profiling using RNA extracted from E11.5 Bmp4 OE mandibles that were induced with dox for 24 hours. Using a 2-fold change (p< 0.05) as threshold, we identified 144 down-regulated and 120 up-regulated genes.