Evidence map›Paper›PMID 25056828›Full record

ArticleNeural development2014

Pioneer midbrain longitudinal axons navigate using a balance of Netrin attraction and Slit repulsion.

Minkyung Kim, W Todd Farmer, Brielle Bjorke, Samuel A McMahon, Pierre J Fabre, Frédéric Charron, Grant S Mastick

Open access · goldAbstract read
In one paragraph

Article in Neural development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 29 citations in OpenAlex.

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  16. Netrin1-DCC-Mediated Attraction Guides Post-Crossing Commissural Axons in the Hindbrain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Minkyung Kim
W Todd Farmer
Brielle Bjorke
Samuel A McMahon
Pierre J Fabre
Frédéric Charron
Grant S MastickDepartment of Biology, University of Nevada, 1664 N Virginia St, Reno, NV 89557, USA. gmastick@unr.edu.
University of Nevada, Reno · USMontreal Clinical Research Institute · CA

Funding

Outreach/Diversity/Pipeline ProjectP20GM103440 · NIGMS · UNIVERSITY OF NEVADA RENO · PI Eduardo A Robleto · 2012 to 2026
$58.0M
UNDERGRADUATE RESEARCH AND TRAININGP20RR016464 · NCRR · UNIVERSITY OF NEVADA RENO · PI REIBER, CARL · 2001 to 2011
$30.3M
Virtual Reality and Augmented Reality CoreP20GM103650 · NIGMS · UNIVERSITY OF NEVADA RENO · PI WEBSTER, MICHAEL A · 2012 to 2022
$20.9M
Cell Biology of Signaling across MembranesP20GM103554 · NIGMS · UNIVERSITY OF NEVADA RENO · PI VON BARTHELD, CHRISTOPHER S · 2012 to 2016
$8.0M
CELL BIOLOGY OF SIGNALING ACROSS MEMBRANESP20RR024210 · NCRR · UNIVERSITY OF NEVADA RENO · PI VON BARTHELD, CHRISTOPHER S · 2011 to 2011
$2.1M
Longitudinal axon guidance by long range cues in the embryonic brainR01NS054740 · NINDS · UNIVERSITY OF NEVADA RENO · PI MASTICK, GRANT STEPHEN · 2008 to 2011
$1.0M
PIONEER AXON GUIDANCE IN THE EMBRYONIC FOREBRAINR01HD038069 · NICHD · UNIVERSITY OF NEVADA RENO · PI MASTICK, GRANT STEPHEN · 2001 to 2004
$800k
Motor neuron migration regulated by guidance cuesR21NS077169 · NINDS · UNIVERSITY OF NEVADA RENO · PI MASTICK, GRANT STEPHEN · 2012 to 2013
$368k
NCRR NIH HHS 1P20 RR024210NCRR NIH HHS P20 RR-016464NICHD NIH HHS HD38069NIGMS NIH HHS 1 P20 GM103650NIGMS NIH HHS 8 P20 GM103440-11NIGMS NIH HHS P20 GM103440NIGMS NIH HHS P20 GM103554NIGMS NIH HHS P20 GM103650NINDS NIH HHS NS054740NINDS NIH HHS NS077169NINDS NIH HHS R01 NS054740NINDS NIH HHS R21 NS077169
6 · The paper itself

Abstract

backgroundLongitudinal axons grow parallel to the embryonic midline to connect distant regions of the central nervous system. Previous studies suggested that repulsive midline signals guide pioneer longitudinal axons by blocking their entry into the floor plate; however, the role of midline attractants, and whether attractant signals may cooperate with repulsive signals, remains unclear. In this study we investigated the navigation of a set of pioneer longitudinal axons, the medial longitudinal fasciculus, in mouse embryos mutant for the Netrin/Deleted in Colorectal Cancer (DCC) attractants, and for Slit repellents, as well as the responses of explanted longitudinal axons in vitro.

resultsIn mutants for Netrin1 chemoattractant or DCC receptor signaling, longitudinal axons shifted away from the ventral midline, suggesting that Netrin1/DCC signals act attractively to pull axons ventrally. Analysis of mutants in the three Slit genes, including Slit1/2/3 triple mutants, suggest that concurrent repulsive Slit/Robo signals push pioneer axons away from the ventral midline. Combinations of mutations between the Netrin and Slit guidance systems provided genetic evidence that the attractive and repulsive signals balance against each other. This balance is demonstrated in vitro using explant culture, finding that the cues can act directly on longitudinal axons. The explants also reveal an unexpected synergy of Netrin1 and Slit2 that promotes outgrowth.

conclusionsThese results support a mechanism in which longitudinal trajectories are positioned by a push-pull balance between opposing Netrin and Slit signals. Our evidence suggests that longitudinal axons respond directly and simultaneously to both attractants and repellents, and that the combined signals constrain axons to grow longitudinally.

Indexed as

ChemotaxisAnimalsAxonsIntercellular Signaling Peptides and ProteinsIntracellular Signaling Peptides and ProteinsMembrane ProteinsMesencephalonMiceMice, TransgenicNerve Growth FactorsNerve Tissue ProteinsNetrin-1NeuronsSlit Homolog 2 ProteinTumor Suppressor ProteinsIntercellular Signaling Peptides and ProteinsIntracellular Signaling Peptides and ProteinsMembrane ProteinsNerve Growth FactorsNerve Tissue ProteinsNetrin-1Slit1 protein, mouseSlit3 protein, mouseSlit Homolog 2 ProteinTumor Suppressor Proteins

Identifiers

PMID25056828
PMCPMC4118263
OpenAlexW2146121941

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.