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The Journal of Neuroscience, June 4, 2008, 28(23):5901-5909; doi:10.1523/JNEUROSCI.1083-08.2008

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Cellular/Molecular
Hepatocyte Growth Factor Regulates Migration of Olfactory Interneuron Precursors in the Rostral Migratory Stream through Met–Grb2 Coupling

Donatella Garzotto,¹ Paolo Giacobini,¹ Tiziana Crepaldi,² Aldo Fasolo,^1,3 and Silvia De Marchis¹

¹Department of Animal and Human Biology, University of Turin, 10123 Turin, Italy, ²Department of Anatomy, Pharmacology, and Forensic Medicine, University of Turin, and ³National Institute of Neuroscience, 10125 Turin, Italy

Correspondence should be addressed to Donatella Garzotto at the above address. Email: donatella.garzotto{at}unito.it

The olfactory bulb is one of the few structures in the mammalian forebrain in which continuous neurogenesis takes place throughout life. Neuronal precursors originate from progenitors located in the subventricular zone (SVZ) of the lateral ventricles, move tangentially in chains through the rostral migratory stream (RMS), and reach the olfactory bulb (OB), where they finally differentiate into granule and glomerular interneurons. Multiple molecular factors are involved in controlling the various steps of this neurogenic process. Here, we show that hepatocyte growth factor (HGF) and its receptor Met protein are expressed in vivo in the OB and throughout the migratory pathway, implying that HGF might mediate migratory signals in this system. By using primary in vitro cultures, we demonstrate that HGF promotes migration of RMS neuroblasts, acting both as an inducer and attractant. HGF stimulation on RMS tissue explants selectively induces MAP kinase pathway activation. Furthermore, in vitro analysis of mice with a point mutation in the Met receptor that impairs signal transduction through the Ras/MAP kinase pathway (Met^Grb2/Grb2) shows that without Met–Grb2 binding, neuroblast migration is reduced. Overall, these findings indicate that HGF signaling via Met–Grb2 coupling influences olfactory interneuron precursor migration along the RMS.

Key words: cell migration; RMS; HGF; olfactory bulb; SVZ; Grb2

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Received Sept. 11, 2007; revised April 21, 2008; accepted April 22, 2008.

Correspondence should be addressed to Donatella Garzotto at the above address. Email: donatella.garzotto{at}unito.it

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