BMPs inhibit neurogenesis by a mechanism involving degradation of a transcription factor

Bone morphogenetic proteins (BMPs), negative regulators of neural determination in the early embryo, were found to be potent inhibitors of neurogenesis in olfactory epithelium (OE) cultures. BMPs 2, 4 or 7 decreased the number of proliferating progenitor cells and blocked production of olfactory receptor neurons (ORNs). Experiments suggested that this effect was due to an action of BMPs on an early-stage progenitor in the ORN lineage. Further analysis revealed that progenitors exposed to BMPs rapidly (< 2 h) lost MASH1, a transcription factor known to be required for the production of ORNs. This disappearance was due to proteolysis of existing MASH1 protein, but new gene expression was required to trigger it. The data suggest a novel mechanism of BMP action, whereby the induced degradation of an essential transcription factor results in premature termination of a neuronal lineage.