Netrin-1 Derived from the Ventricular Zone, but not the Floor Plate, Directs Hindbrain Commissural Axons to the Ventral Midline

Netrin-1 (Ntn1) emanating from the ventral midline has been thought to act as a long-range diffusible chemoattractant for commissural axons (CAs). However, CAs still grow towards the midline in the absence of the floor plate (FP), a glial structure occupying the midline. Here, using genetically loss...

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Bibliographic Details
Published in:Scientific reports 2017-09, Vol.7 (1), p.11992-12, Article 11992
Main Authors: Yamauchi, Kenta, Yamazaki, Maya, Abe, Manabu, Sakimura, Kenji, Lickert, Heiko, Kawasaki, Takahiko, Murakami, Fujio, Hirata, Tatsumi
Format: Article
Language:English
Subjects:
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Animals
Axons - physiology
Chemotactic Factors - metabolism
Conditional mutant
Female
Floor plate
Hindbrain
Humanities and Social Sciences
Male
Mice, Inbred C57BL
multidisciplinary
Netrin-1
Netrin-1 - metabolism
Neural Tube - metabolism
Rhombencephalon - embryology
Science
Science (multidisciplinary)
Spinal cord
Ventricle
Ventricular zone
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Summary:Netrin-1 (Ntn1) emanating from the ventral midline has been thought to act as a long-range diffusible chemoattractant for commissural axons (CAs). However, CAs still grow towards the midline in the absence of the floor plate (FP), a glial structure occupying the midline. Here, using genetically loss-of-function approaches in mice, we show that Ntn1 derived from the ventricular zone (VZ), but not the FP, is crucial for CA guidance in the mouse hindbrain. During the period of CA growth, Ntn1 is expressed in the ventral two-thirds of the VZ, in addition to the FP. Remarkably, deletion of Ntn1 from the VZ and even from the dorsal VZ highly disrupts CA guidance to the midline, whereas the deletion from the FP has little impact on it. We also show that the severities of CA guidance defects found in the Ntn1 conditional mutants were irrelevant to their FP long-range chemoattractive activities. Our results are incompatible with the prevailing view that Ntn1 is an FP-derived long-range diffusible chemoattractant for CAs, but suggest a novel mechanism that VZ-derived Ntn1 directs CAs to the ventral midline by its local actions.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-12269-8