BMP11 - A candidate negative regulator of olfactory neurogenesis.

47. BMP1i—A Candidate Negative Regulator of Olfactory Neuro- genesis. H.-H. Wu.‘ P. Chem.‘ J. E. Johnson.’f and A. L. Calof.‘ ‘Department of Anatomy and Neurobiology. UC Irvine. Irvine. California 926974275: and TUT Southwestern. Dallas. Texas 75390. In vivo studies suggest that olfactory epithelium (OE) neurogenv esis is regulated by signals produced by olfactory receptor neurons (ORNs). which inhibit proliferation of neuronal progenitors. This hypothesis is supported by experiments showing that OE neuronal progenitors cultured with high numbers of 0RNs generate fewer neurons. Some BMPs also act in this way: BMPs 2. 4. and 7 act on neuronal progenitors in the ORN lineage to inhibit neurogenesis. Nevertheless. in the olfactory mucosa. these BMPs are not ex- pressed exclusively in ORNs. Therefore, other negative regulators may be important in OE neurogenesis. One candidate is BMPI I. In situ hybridization shows that Bmpll is exclusively expressed in GE. but not in adjacent stroma or respiratory epithelium. BMPil belongs to a class of BMPs that includes the negative regulator of muscle growth. CDF8. Since CDF8 is 90% identical to BMPI l. we tested CDF8 effects on OE neurogenesis. CDF8 strongly inhibits neurogenesis in a dose-dependent manner. Unlike BMPs 2. 4, and 7. however. CDF8 treatment has no effect on MASHl+ progenitors. suggesting that CDF8 acts at a different cell stage or through a different signaling pathway. Experiments with OE cultured from GFP reporter mice suggest that CDF8 inhibits development of Ngnl-expressing immediate neuronal precursors. the progeny of MASHl+ progenitors. Current experiments are directed toward identifying the receptors that mediate this action and determining whether OE responses to other growth factors are affected by CDF 8 signaling. (Supported by NIH Grants DC03583 and HD3876! to A.L.C.)