Opposing effects of bone morphogenetic proteins on neuron production and survival in the olfactory receptor neuron lineage

In olfactory epithelium (OE) cultures, bone morphogenetic proteins (BMPs) c an strongly inhibit neurogenesis, Here we provide evidence that BMPs also p romote, and indeed are required, for OE neurogenesis. Addition of the BMP a ntagonist noggin inhibited neurogenesis in OE-stromal cell co-cultures. Bmp 2, Bmp4 and Bmp7 were expressed by OE stroma, and low concentrations of BMP 4 (below the threshold for inhibition of neurogenesis) stimulated neurogene sis; BMP7 did not exhibit a stimulatory effect at any concentration tested. Stromal cell conditioned medium also stimulated neurogenesis; part of this effect was due to the presence within it of a noggin-binding factor or fac tors. Studies of the pro-neurogenic effect of BMP4 indicated that it did no t increase progenitor cell proliferation, but rather promoted survival of n ewly generated olfactory receptor neurons. These findings indicate that BMP s exert both positive and negative effects on neurogenesis, depending on li gand identity, ligand concentration and the particular cell in the lineage that is responding, In addition, they reveal the presence of a factor or fa ctors, produced by OE stroma, that can synergize with BMP4 to stimulate OE neurogenesis.