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oai:repisalud.isciii.es:20.500.12105/65212024-09-27T09:15:21Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Bhardwaj, Deepshikha author Nager, Mireia author Camats, Judith author David, Monica author Benguria, Alberto author Dopazo, Ana author Canti, Carles author Herreros, Judit author 2013 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. Front Cell Neurosci. 2013; 7:52 10.3389/fncel.2013.00052 1662-5102 Frontiers in Cellular Neuroscience 23641195 http://hdl.handle.net/20.500.12105/6521 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 Chemokines induce axon outgrowth downstream of Hepatocyte Growth Factor and TCF/beta-catenin signaling