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Neuron. 2019 Feb 20;101(4):635-647.e4. doi: 10.1016/j.neuron.2018.12.025. Epub 2019 Jan 17.

Long-Range Guidance of Spinal Commissural Axons by Netrin1 and Sonic Hedgehog from Midline Floor Plate Cells.

Author information

1
Laboratory of Brain Development and Repair, The Rockefeller University, New York, NY 10065, USA.
2
Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 2B4, Canada.
3
Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada.
4
Sorbonne Université, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France.
5
Montreal Clinical Research Institute (IRCM), 110 Pine Avenue West, Montreal, QC H2W 1R7, Canada; Integrated Program in Neuroscience, McGill University, Montreal, QC H3A 2B4, Canada; Division of Experimental Medicine, Department of Anatomy and Cell Biology, Department of Biology, McGill University, Montreal, QC H3A 2B2, Canada; Department of Medicine, University of Montreal, Montreal, QC H3T 1J4, Canada. Electronic address: frederic.charron@ircm.qc.ca.
6
Laboratory of Brain Development and Repair, The Rockefeller University, New York, NY 10065, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA. Electronic address: tessier3@stanford.edu.

Abstract

An important model for axon pathfinding is provided by guidance of embryonic commissural axons from dorsal spinal cord to ventral midline floor plate (FP). FP cells produce a chemoattractive activity, comprised largely of netrin1 (FP-netrin1) and Sonic hedgehog (Shh), that can attract the axons at a distance in vitro. netrin1 is also produced by ventricular zone (VZ) progenitors along the axons' route (VZ-netrin1). Recent studies using region-specific netrin1 deletion suggested that FP-netrin1 is dispensable and VZ-netrin1 sufficient for netrin guidance activity in vivo. We show that removing FP-netrin1 actually causes guidance defects in spinal cord consistent with long-range action (i.e., over hundreds of micrometers), and double mutant analysis supports that FP-netrin1 and Shh collaborate to attract at long range. We further provide evidence that netrin1 may guide via chemotaxis or haptotaxis. These results support the model that netrin1 signals at both short and long range to guide commissural axons in spinal cord.

KEYWORDS:

Netrin1; Sonic hedgehog; axon guidance; chemoattraction; commissural neurons; floor plate; haptotaxis; long-range guidance; neural tube; spinal cord

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