Blitz, IL

Calof, AL

Murray, RC

Wineland, A

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UC IrvineUC Irvine Previously Published WorksTitleA transgenic approach for determining the role of bone morphogenetic proteins in the development of olfactory receptor neurons.Permalinkhttps://escholarship.org/uc/item/6cw8n63gJournalDEVELOPMENTAL BIOLOGY, 271(2)ISSN0012-1606AuthorsWineland, ABlitz, ILMurray, RCet al.Publication Date2004Copyright InformationThis work is made available under the terms of a Creative Commons Attribution License, availalbe at https://creativecommons.org/licenses/by/4.0/ Peer reviewedeScholarship.org Powered by the California Digital LibraryUniversity of California275. A Transgenic Approach for Determining the Role of BoneMorphogenetic Proteins in the Development of Olfactory Recep-tor Neurons. André Wineland,1 Ira L. Blitz,2 Richard C. Murray,1and Anne L. Calof2. 1Hendrix College, Conway, AR 72032; 2Univ. ofCalifornia, Irvine, CA 92697.Mouse olfactory receptor neurons (ORNs) are generated throughout lifefrom progenitor cells that reside within the olfactory epithelium (OE).Proliferation of progenitors and survival of ORNs are positively andnegatively regulated by bone morphogenetic proteins (BMPs) in vitroand several Bmps are expressed in and around the OE (Shou et al., 2000,Development 127, 5403) suggesting that BMPs may regulate olfactoryneurogenesis in vivo. To test this, we generated transgenic mice thatoverexpress BMP4 or Noggin in the OE to alter intrinsic BMP signaling.To allow detection of the proteins, Bmp4 and noggin cDNAs were epitope-tagged and demonstrated to be functional and properly secreted. Expressionwas directed to ORNs using the tissue-specific genomic regulatory elementsfrom the Omp gene (Danciger et al., 1989, PNAS 86, 8565). Ten Omp-Bmp4 and eight Omp-Noggin lines were generated and transgene expres-sion was demonstrated using RT-PCR, immunoblotting, or histochemistry.The line with the highest level of expression was chosen for furtheranalysis. Decreased numbers of both proliferating progenitors and apoptoticcells were detected in the OE of both types of transgenics. In addition, theOE of Omp-Bmp4 transgenics showed decreases in ORN number and OEthickness, and altered expression of GAP43, a phosphoprotein involved inneuron maturation and axon growth. These findings demonstrate thatregulation of BMP levels is crucial to the development and maintenanceof neuron number in the OE, and suggest that BMPs also regulate the rateof ORN turnover. (Supported by grants to ALC: NIH (DC-03583 and HD-38761) and MOD.)

A transgenic approach for determining the role of bone morphogenetic proteins in the development of olfactory receptor neurons.

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