Directed growth of early cortical axons is influenced by a chemoattractant released from an intermediate target

Richards, LJ, Koester, SE, Tuttle, R and OLeary, DDM (1997) Directed growth of early cortical axons is influenced by a chemoattractant released from an intermediate target. Journal of Neuroscience, 17 7: 2445-2458.

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Author Richards, LJ
Koester, SE
Tuttle, R
OLeary, DDM
Title Directed growth of early cortical axons is influenced by a chemoattractant released from an intermediate target
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 1997-04-01
Year available 1997
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 17
Issue 7
Start page 2445
End page 2458
Total pages 14
Place of publication WASHINGTON
Publisher SOC NEUROSCIENCE
Language eng
Abstract Projection neurons throughout the mature mammalian neocortex extend efferent axons either through the ventrolaterally positioned internal capsule to subcortical targets or through the dorsally located midline corpus callosum to the contralateral cortex. In rats, the internal capsule is pioneered on E14, but the corpus callosum is not pioneered until E17, even though these two types of projection neurons are generated at the same time. Here we use axonal markers to demonstrate that early cortical axon growth is directed toward the nascent internal capsule, which could account for the timing difference in the development of the two efferent pathways, This directed axon growth may be due to a chemoattractant and/or a chemorepellent secreted by intermediate targets of corlical efferent axons, the nascent internal capsule, or the medial wall of the dorsal telencephalon (MDT), respectively, To test for these soluble activities, explants of E15 rat neocortex and intermediate targets were cocultured in collagen gels. Cortical axon outgrowth was directed toward the internal capsule, but outgrowth was nondirected and suppressed when cocultured with MDT, suggesting that the internal capsule releases a chemoattractant for cortical axons, whereas the MDT releases a chemosuppressant. Because the chemoattractant Netrin-1 is expressed in the internal capsule, we cocultured cortical explants with E13 rat floor plate, which expresses Netrin-1, or with Netrin-1-transfected or control-transfected 293T cells. Cortical axon growth was directed toward both floor plate and Netrin-1-transfected 293T cells, as it had been toward the internal capsule, but not toward control-transfected 293T cells. These findings suggest that early events in cortical axon pathfinding may be controlled by a soluble activity which attracts initial axon growth toward the internal capsule and that this activity may be due to Netrin-1.
Keyword axon guidance
axon pathfinding
chemorepellent
chemosuppression
cortical development
cortical efferents
corpus callosum
subplate
internal capsule
Netrin
Central-Nervous-System
Floor Plate
Chondroitin Sulfate
Commissural Axons
Motor Axons
Mouse-Brain
Rat
Cells
Neocortex
Pathway
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID NS31558
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: ResearcherID Downloads - Archived
 
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