Neogenin May Functionally Substitute for Dcc in Chicken

Phan, Keith D.; Croteau, Louis-Philippe; Kam, Joseph Wai Keung; Kania, Artur; Cloutier, Jean-François; Butler, Samantha J.

doi:10.1371/journal.pone.0022072

Cited by 35 publications

(45 citation statements)

References 49 publications

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“…Dcc is widely expressed in postmitotic neurons in the spinal cord (Figure S2A) and Dcc protein decorates a broad population of commissural axons (Figures S2D–S2F) (Phan et al, 2011). Of the Unc5 family, only Unc5a and Unc5c have detectable expression in postmitotic neurons in the spinal cord (Figures S2B–S2C) (Engelkamp, 2002; Leonardo et al, 1997; Masuda et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

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

Varadarajan

Kong

Phan

et al. 2017

Neuron

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161

193

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SUMMARY 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.

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Section: Resultsmentioning

confidence: 99%

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

Varadarajan

Kong

Phan

et al. 2017

Neuron

Self Cite

161

193

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show abstract

“…Various molecular interactions between the two pathways allow for a fine-tuning between attraction and repulsion (Ché dotal, 2011). Surprisingly, although these mechanisms are largely conserved among species, a DCC ortholog appears to be absent from the chicken genome (Phan et al, 2011), and the commissureless proteins, which are negative modulators of Slit/Robo signaling in the Drosophila nerve cord, might exist only in Diptera (Sarro et al, 2013). This suggests that commissural axon guidance mechanisms may be more diverse across species than previously appreciated.…”

Section: Introductionmentioning

confidence: 99%

Signaling Switch of the Axon Guidance Receptor Robo3 during Vertebrate Evolution

Zelina¹,

Blockus²,

Zagar³

et al. 2014

Neuron

146

198

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Development of neuronal circuits is controlled by evolutionarily conserved axon guidance molecules, including Slits, the repulsive ligands for roundabout (Robo) receptors, and Netrin-1, which mediates attraction through the DCC receptor. We discovered that the Robo3 receptor fundamentally changed its mechanism of action during mammalian evolution. Unlike other Robo receptors, mammalian Robo3 is not a high-affinity receptor for Slits because of specific substitutions in the first immunoglobulin domain. Instead, Netrin-1 selectively triggers phosphorylation of mammalian Robo3 via Src kinases. Robo3 does not bind Netrin-1 directly but interacts with DCC. Netrin-1 fails to attract pontine neurons lacking Robo3, and attraction can be restored in Robo3(-/-) mice by expression of mammalian, but not nonmammalian, Robo3. We propose that Robo3 evolution was key to sculpting the mammalian brain by converting a receptor for Slit repulsion into one that both silences Slit repulsion and potentiates Netrin attraction.

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“…By in situ hybridization and immunohistochemistry, Dcc expression is observed in interneurons and motor neurons, as well as in neuroprogenitors [4, 5, 27, 28]. Robo3 expression is more specific and mostly within commissural interneurons [20, 23].…”

Section: Resultsmentioning

confidence: 99%

Netrin1/DCC signaling promotes neuronal migration in the dorsal spinal cord

et al. 2016

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BackgroundNewborn neurons often migrate before undergoing final differentiation, extending neurites, and forming synaptic connections. Therefore, neuronal migration is crucial for establishing neural circuitry during development. In the developing spinal cord, neuroprogenitors first undergo radial migration within the ventricular zone. Differentiated neurons continue to migrate tangentially before reaching the final positions. The molecular pathways that regulate these migration processes remain largely unknown. Our previous study suggests that the DCC receptor is important for the migration of the dorsal spinal cord progenitors and interneurons. In this study, we determined the involvement of the Netrin1 ligand and the ROBO3 coreceptor in the migration.ResultsBy pulse labeling neuroprogenitors with electroporation, we examined their radial migration in Netrin1 (Ntn1), Dcc, and Robo3 knockout mice. We found that all three mutants exhibit delayed migration. Furthermore, using immunohistochemistry of the BARHL2 interneuron marker, we found that the mediolateral and dorsoventral migration of differentiated dorsal interneurons is also delayed. Together, our results suggest that Netrin1/DCC signaling induce neuronal migration in the dorsal spinal cord.ConclusionsNetrin1, DCC, and ROBO3 have been extensively studied for their functions in regulating axon guidance in the spinal commissural interneurons. We reveal that during earlier development of dorsal interneurons including commissural neurons, these molecules play an important role in promoting cell migration.Electronic supplementary materialThe online version of this article (doi:10.1186/s13064-016-0074-x) contains supplementary material, which is available to authorized users.

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Neogenin May Functionally Substitute for Dcc in Chicken

Cited by 35 publications

References 49 publications

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

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

Signaling Switch of the Axon Guidance Receptor Robo3 during Vertebrate Evolution

Netrin1/DCC signaling promotes neuronal migration in the dorsal spinal cord

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