@article{7e6576469de846e38ec53fd1d583a445,
title = "Netrin1 Produced by Neural Progenitors, Not Floor Plate Cells, Is Required for Axon Guidance in the Spinal Cord",
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",
author = "Varadarajan, {Supraja G.} and Kong, {Jennifer H.} and Phan, {Keith D.} and Kao, {Tzu Jen} and Panaitof, {S. Carmen} and Julie Cardin and Holger Eltzschig and Artur Kania and Novitch, {Bennett G.} and Butler, {Samantha J.}",
note = "Funding Information: We are most grateful to Alex Joyner and Marc Tessier-Lavigne for the gifts of mutant mice and for Joe Herrold and Anna Maria Maglunog for early technical assistance. We would also like to thank James Briscoe, Greg Bashaw, Orkun Akin, and Larry Zipursky for invaluable discussions and comments on the manuscript. This work was supported by grants from the National Institute of Health (NIH) (DK097075, HL098294, HL114457, DK082509, HL109233, DK109574, HL119837, and HL133900) to H.E., Canadian Institutes of Health Research (MOP-97758 and MOP-77556), Brain Canada, Natural Sciences and Engineering Research Council, Canadian Foundation for Innovation, and the W. Garfield Weston Foundation to A.K., the March of Dimes Foundation (6-FY10-296) and National Institute of Health (NIH) (NS072804, NS089817, and NS085227) to B.G.N., and the March of Dimes (1-FY07-458), the NIH (NS063999 and NS085097), and the UCLA Broad Stem Cell Research Center to S.J.B. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = may,
day = "17",
doi = "10.1016/j.neuron.2017.03.007",
language = "English",
volume = "94",
pages = "790--799.e3",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "4",
}