Chemokines induce axon outgrowth downstream of Hepatocyte Growth Factor and TCF/beta-catenin signaling

Axon morphogenesis is a complex process regulated by a variety of secreted molecules, including morphogens and growth factors, resulting in the establishment of the neuronal circuitry. Our previous work demonstrated that growth factors [Neurotrophins (NT) and Hepatocyte Growth Factor (HGF)] signal t...

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Detalles Bibliográficos
Autores: Bhardwaj, Deepshikha, Nager, Mireia, Camats, Judith, David, Monica, Benguria, Alberto, Dopazo, Ana, Canti, Carles, Herreros, Judit
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6521
Acceso en línea:http://hdl.handle.net/20.500.12105/6521
Access Level:acceso abierto
Palabra clave:Beta-catenin
Axon
Neurite outgrowth
Chemokine
Hippocampal neurons
Hepatocyte growth factor
CELL-DERIVED FACTOR-1
BETA-CATENIN
INTERNEURON MIGRATION
HIPPOCAMPAL-NEURONS
NEURITE OUTGROWTH
SYNAPSE FORMATION
NERVOUS-SYSTEM
DENTATE GYRUS
RECEPTORS
CXCR4
Descripción
Sumario:Axon morphogenesis is a complex process regulated by a variety of secreted molecules, including morphogens and growth factors, resulting in the establishment of the neuronal circuitry. Our previous work demonstrated that growth factors [Neurotrophins (NT) and Hepatocyte Growth Factor (HGF)] signal through beta-catenin during axon morphogenesis. HGF signaling promotes axon outgrowth and branching by inducing beta-catenin phosphorylation at Y142 and transcriptional regulation of T-Cell Factor (TCF) target genes. Here, we asked which genes are regulated by HGF signaling during axon morphogenesis. An array screening indicated that HGF signaling elevates the expression of chemokines of the CC and CXC families. In line with this, CCL7, CCL20, and CXCL2 significantly increase axon outgrowth in hippocampal neurons. Experiments using blocking antibodies and chemokine receptor antagonists demonstrate that chemokines act downstream of HGF signaling during axon morphogenesis. In addition, qPCR data demonstrates that CXCL2 and CCL5 expression is stimulated by HGF through Met/b-catenin/TCF pathway. These results identify CC family members and CXCL2 chemokines as novel regulators of axon morphogenesis downstream of HGF signaling.

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