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Volume 16, Number 21, Issue of November 1, 1996 pp. 6933-6944
Copyright ©1996 Society for Neuroscience

Expression of Hepatocyte Growth Factor/Scatter Factor, Its Receptor, c-met, and Tissue-Type Plasminogen Activator during Development of the Murine Olfactory System

Received May 22, 1996; revised Aug. 15, 1996; accepted Aug. 19, 1996.

Douglas P. Thewke and Nicholas W. Seeds

Neuroscience Program and Department of Biochemistry/Biophysics and Genetics, University of Colorado Health Sciences Center, Denver, Colorado 80262

The expression of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the c-met proto-oncogene product, was examined by in situ hybridization in the developing and adult murine olfactory system and compared with the expression of a known activator of HGF/SF, tissue-type plasminogen activator (tPA). In the developing olfactory canal, expression of both c-met and tPA was observed in the olfactory neuroepithelium, whereas HGF/SF expression appeared to be confined to the mucosa adjacent to the neuroepithelium. During development of the olfactory bulb, HGF/SF and tPA were expressed within the rostral migratory pathway leading to the olfactory bulb, whereas c-met expression was observed in the mitral cell layer (MCL) of the olfactory bulb and in the anterior olfactory nucleus. In the adult olfactory bulb, expression of HGF/SF was restricted to the periglomerular region of the glomerular layer, whereas c-met was expressed in the MCL and olfactory nerve fiber layers (ONL). tPA expression in the adult olfactory bulb was observed in the ONL, MCL, and granule cell layers. Therefore, tPA expression was relatively coincident with the expression of HGF/SF and/or c-met in the appropriate projection patterns of the developing and adult olfactory system. In addition, antibodies against tPA inhibited the olfactory bulb extract-mediated cleavage of single-chain HGF/SF. These results suggest that tPA may play a regulatory role in the development and maintenance of the olfactory system by activating HGF/SF in the immediate vicinity of its receptor.

Key words: hepatocyte growth factor; c-met; tissue-type plasminogen activator; olfactory system; olfactory bulb

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