HGF regulates the development of cortical pyramidal dendrites.
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.
Gutierrez
Humberto
H
Department Preclinical Veterinary Sciences, Royal (Dick) Studies, University of Edinburgh, Summerhall Square, Edinburgh EH9 1QH, UK. humberto.g@ed.ac.uk
Dolcet
Xavier
X
Tolcos
Mary
M
Davies
Alun
A
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D016764:Cell Polarity; D048429:Cell Size; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D046508:Culture Techniques; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met