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First published online 30 June 2004
doi: 10.1242/dev.01209

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HGF regulates the development of cortical pyramidal dendrites

Humberto Gutierrez^1,*,, Xavier Dolcet^1,, Mary Tolcos^1, and Alun Davies^1,*

¹ Department Preclinical Veterinary Sciences, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Summerhall Square, Edinburgh EH9 1QH, UK

Author for correspondence (e-mail: humberto.g{at}ed.ac.uk)

Accepted 7 April 2004

Although hepatocyte growth factor (HGF) and its receptor tyrosine kinase MET are widely expressed in the developing and mature central nervous system, little is known about the role of MET signaling in the brain. We have used particle-mediated gene transfer in cortical organotypic slice cultures established from early postnatal mice to study the effects of HGF on the development of dendritic arbors of pyramidal neurons. Compared with untreated control cultures, exogenous HGF promoted a highly significant increase in dendritic growth and branching of layer 2 pyramidal neurons, whereas inactivation of endogenous HGF with function-blocking, anti-HGF antibody caused a marked reduction in size and complexity of the dendritic arbors of these neurons. Furthermore, pyramidal neurons transfected with an MET dominant-negative mutant receptor likewise had much smaller and less complex dendritic arbors than did control transfected neurons. Our results indicate that HGF plays a role in regulating dendritic morphology in the developing cerebral cortex.

Key words: MET, c-MET, Neurons, Process growth, GFP, Slice cultures

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