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Neuron. 2017 May 17;94(4):790-799.e3. doi: 10.1016/j.neuron.2017.03.007. Epub 2017 Apr 21.

Netrin1 Produced by Neural Progenitors, Not Floor Plate Cells, Is Required for Axon Guidance in the Spinal Cord.

Author information

1
Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Neuroscience Interdisciplinary Graduate Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
2
Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
3
Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, QC H2W 1R7, Canada; Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology and Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei, Taiwan.
4
Department of Biology, University of Nebraska, Kearney, Kearney, NE 68849, USA.
5
Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology and Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei, Taiwan.
6
Department of Anesthesiology, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX 77030, USA.
7
Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, QC H2W 1R7, Canada; Faculté de Médecine, Université de Montréal, Montréal, QC H3C 3J7, Canada; Departments of Anatomy and Cell Biology and Biology, Division of Experimental Medicine, McGill University, Montréal, QC H3A 3R1, Canada.
8
Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Neuroscience Interdisciplinary Graduate Program, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: butlersj@ucla.edu.

Abstract

Netrin1 has been proposed to act from the floor plate (FP) as a long-range diffusible chemoattractant for commissural axons in the embryonic spinal cord. However, netrin1 mRNA and protein are also present in neural progenitors within the ventricular zone (VZ), raising the question of which source of netrin1 promotes ventrally directed axon growth. Here, we use genetic approaches in mice to selectively remove netrin from different regions of the spinal cord. Our analyses show that the FP is not the source of netrin1 directing axons to the ventral midline, while local VZ-supplied netrin1 is required for this step. Furthermore, rather than being present in a gradient, netrin1 protein accumulates on the pial surface adjacent to the path of commissural axon extension. Thus, netrin1 does not act as a long-range secreted chemoattractant for commissural spinal axons but instead promotes ventrally directed axon outgrowth by haptotaxis, i.e., directed growth along an adhesive surface.

KEYWORDS:

adhesion; axon guidance; chemotaxis; dcc; floor plate; haptotaxis; netrin1; progenitors; spinal cord; ventricular zone

PMID:
28434801
PMCID:
PMC5576449
DOI:
10.1016/j.neuron.2017.03.007
[Indexed for MEDLINE]
Free PMC Article

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