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Neuronal Cell Bodies Remotely Regulate Axonal Growth Response to Localized Netrin-1 Treatment via Second Messenger and DCC Dynamics
Author(s)
Date Issued
2017-01-05
Date Available
2019-01-30T16:10:16Z
Abstract
Netrin-1 modulates axonal growth direction and speed. Its best characterized receptor, Deleted in Colorectal Cancer (DCC), is localized to growth cones, but also observed in the cell bodies. We hypothesized that cell bodies sense Netrin-1 and contribute to axon growth rate modulation, mediated by the second messenger system. We cultured mouse cortical neurons in microfluidic devices to isolate distal axon and cell body microenvironments. Compared to isolated axonal treatment, global Netrin-1 treatment decreased the axon elongation rate and affected the dynamics of total and membranous DCC, calcium, and cyclic nucleotides. Signals induced by locally applied Netrin-1 propagated in both anterograde and retrograde directions, demonstrated by the long-range increase in DCC and by the increased frequency of calcium transients in cell bodies, evoked by axonal Netrin-1. Blocking the calcium efflux from endoplasmic reticulum suppressed the membranous DCC response. Our findings support the notion that neurons sense Netrin-1 along their entire lengths in making axonal growth decisions.
Sponsorship
European Commission - European Regional Development Fund
Science Foundation Ireland
Other Sponsorship
Nanoremedies Programme
Marie-Curie Intra-European Fellowship
AXA Research Fund Doctoral Fellowship
Type of Material
Journal Article
Publisher
Frontiers
Journal
Frontiers in Cellular Neuroscience
Volume
10
Issue
298
Copyright (Published Version)
2018 the Authors
Language
English
Status of Item
Peer reviewed
ISSN
1662-5102
This item is made available under a Creative Commons License
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Neuronal Cell Bodies Remotely Regulate Axonal Growth Response to Localized Netrin-1 Treatment via Second Messenger and DCC Dynamics.pdf
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7.11 MB
Format
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