Sema-1a Reverse Signaling Promotes Midline Crossing in Response to Secreted Semaphorins

Hernandez-Fleming, Melissa; Rohrbach, Ethan W.; Bashaw, Greg J.

doi:10.1016/j.celrep.2016.12.027

Cited by 25 publications

(16 citation statements)

References 56 publications

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“…Several studies have shown that the signalling activities and interactions of class-6 semaphorins are regulated by a complex combination of cis-and trans-interactions with plexin A receptors (Haklai-Topper et al, 2010;Andermatt et al, 2014;Perez-Branguli et al, 2016). A role for membranebound Semaphorin 1a has also been shown for midline crossing in invertebrates, although in this case the effect was found to be independent of Plexin binding (Hernandez-Fleming et al, 2017).…”

Section: Regulation At the Post-translational Levelmentioning

confidence: 98%

Understanding axon guidance: are we nearly there yet?

2018

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During nervous system development, neurons extend axons to reach their targets and form functional circuits. The faulty assembly or disintegration of such circuits results in disorders of the nervous system. Thus, understanding the molecular mechanisms that guide axons and lead to neural circuit formation is of interest not only to developmental neuroscientists but also for a better comprehension of neural disorders. Recent studies have demonstrated how crosstalk between different families of guidance receptors can regulate axonal navigation at choice points, and how changes in growth cone behaviour at intermediate targets require changes in the surface expression of receptors. These changes can be achieved by a variety of mechanisms, including transcription, translation, protein-protein interactions, and the specific trafficking of proteins and mRNAs. Here, I review these axon guidance mechanisms, highlighting the most recent advances in the field that challenge the textbook model of axon guidance.

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Section: Regulation At the Post-translational Levelmentioning

confidence: 98%

Understanding axon guidance: are we nearly there yet?

2018

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“…In vitro, contextdependent switch from attraction to repulsion and vice-versa were evidenced for a large range of guidance molecules including Netrins, Semaphorins, and Slits (Höpker et al, 1999;Castellani et al, 2000;Nguyen-Ba-Charvet et al, 2001;Castellani et al, 2002;Ma et al, 2007). In vivo, although considered as repellents, Sema2a and Sema3B were recently reported to promote midline crossing in drosophila, acting as chemoattractant via Sema1a (Hernandez-Fleming et al, 2017).…”

Section: Commissural Axon Navigation Is Driven By Restriction Of Growmentioning

confidence: 99%

Iterative inhibition of commissural growth cone exploration, not post-crossing barrier, ensures forward midline navigation through SlitC-PlxnA1 signaling

Ducuing

Gardette

Pignata

et al. 2020

Preprint

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Sensitization to Slits and Semaphorin (Sema)3B floor plate repellents after midline crossing is thought to be the mechanism expelling commissural axons contralaterally and preventing their back-turning. We studied the role of Slit-C terminal fragment sharing with Sema3B the Plexin (Plxn) A1 receptor, newly implicated in midline guidance. We generated a knock-in mouse strain baring PlxnA1Y1815F mutation altering SlitC but not Sema3B responses and observed recrossing phenotypes. Using fluorescent reporters, we found that Slits and Sema3B form clusters decorating an unexpectedly complex mesh of ramified FP glia basal processes spanning the entire navigation path. Time-lapse analyzes revealed that impaired SlitC sensitivity destabilized axon trajectories by inducing high levels of growth cone exploration from the floor plate entry, increasing risk of aberrant decisions. Thus, FP crossing is unlikely driven by post-crossing sensitization to SlitC. Rather, SlitC limits growth cone plasticity and exploration through reiterated contacts, continuously imposing a straight and forward-directed trajectory.

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“…This indicates that additional pathways must promote midline crossing [ 11 , 12 ]. Indeed, several additional factors implicated in promoting midline axon attraction have been identified in invertebrate and vertebrate systems, such as Shh/Boc [ 13 ], Sema2a/Sema1a [ 14 ], and VEGF/Flk1 [ 15 ]. In addition, many other mechanisms have been described that promote axon growth across the midline by preventing premature responses to repulsive molecules secreted from the midline, such as Slits and Semaphorins [ 16 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

Brain Tumor promotes axon growth across the midline through interactions with the microtubule stabilizing protein Apc2

Arbeille

Bashaw

2018

PLoS Genet

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Commissural axons must cross the midline to establish reciprocal connections between the two sides of the body. This process is highly conserved between invertebrates and vertebrates and depends on guidance cues and their receptors to instruct axon trajectories. The DCC family receptor Frazzled (Fra) signals chemoattraction and promotes midline crossing in response to its ligand Netrin. However, in Netrin or fra mutants, the loss of crossing is incomplete, suggesting the existence of additional pathways. Here, we identify Brain Tumor (Brat), a tripartite motif protein, as a new regulator of midline crossing in the Drosophila CNS. Genetic analysis indicates that Brat acts independently of the Netrin/Fra pathway. In addition, we show that through its B-Box domains, Brat acts cell autonomously to regulate the expression and localization of Adenomatous polyposis coli-2 (Apc2), a key component of the Wnt canonical signaling pathway, to promote axon growth across the midline. Genetic evidence indicates that the role of Brat and Apc2 to promote axon growth across the midline is independent of Wnt and Beta-catenin-mediated transcriptional regulation. Instead, we propose that Brat promotes midline crossing through directing the localization or stability of Apc2 at the plus ends of microtubules in navigating commissural axons. These findings define a new mechanism in the coordination of axon growth and guidance at the midline.

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Sema-1a Reverse Signaling Promotes Midline Crossing in Response to Secreted Semaphorins

Cited by 25 publications

References 56 publications

Understanding axon guidance: are we nearly there yet?

Understanding axon guidance: are we nearly there yet?

Iterative inhibition of commissural growth cone exploration, not post-crossing barrier, ensures forward midline navigation through SlitC-PlxnA1 signaling

Brain Tumor promotes axon growth across the midline through interactions with the microtubule stabilizing protein Apc2

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