Year-end Sale % OFF 
Abstract
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 β-catenin during axon morphogenesis. HGF signaling promotes axon outgrowth and branching by inducing β-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.
Highlights
The establishment of the neuronal morphogenesis is a complex process by which neurons extend and branch out an axon and dendrites, resulting in the proper assembly of the neuronal circuitry
CHEMOKINES OF THE CC AND CXC FAMILIES ARE UPREGULATED BY Hepatocyte Growth Factor (HGF) TREATMENT Previous work demonstrated that HGF signals through phosphorylation of β-catenin at Y142 (PY142) β-catenin and TCF4 to regulate the expression of target genes
Aiming to identify the genes regulated by HGF signaling in developing hippocampal neurons during axon morphogenesis, we found the upregulation of several chemokines of the CC and CXC families
Summary
The establishment of the neuronal morphogenesis is a complex process by which neurons extend and branch out an axon and dendrites, resulting in the proper assembly of the neuronal circuitry. HGF signaling induces the phosphorylation of β-catenin at Y142 (PY142), which translocates to the nucleus and promotes axon morphogenesis through TCF4/β-catenin-dependent transcription of target genes (David et al, 2008). These findings highlight the relevance of β-catenin forms producing transcriptional regulation independent of Wnt signaling (Monga et al, 2002; Zeng et al, 2006; Heuberger and Birchmeier, 2010; Xi et al, 2012)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
