scholarly journals Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements

Cell Reports ◽  
2021 ◽  
Vol 34 (3) ◽  
pp. 108654
Author(s):  
Oriane Pourchet ◽  
Marie-Pierre Morel ◽  
Quentin Welniarz ◽  
Nadège Sarrazin ◽  
Fabio Marti ◽  
...  
Keyword(s):  
Floor Plate ◽  
Mirror Movements ◽  
Midline Crossing

scholarly journals Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements

2020 ◽  
Author(s):  
Oriane Pourchet ◽  
Marie-Pierre Morel ◽  
Quentin Welniarz ◽  
Nadège Sarrazin ◽  
Fabio Marti ◽  
...  
Keyword(s):  
Motor Control ◽  
Primary Motor Cortex ◽  
Motor Command ◽  
Floor Plate ◽  
Knock Out ◽  
Mirror Movements ◽  
Midline Crossing ◽  
Contralateral Hand ◽  
Functional Consequences ◽  
Knock Out Mice

AbstractIn human, execution of unimanual movements requires lateralized activation of the primary motor cortex, which then transmits the motor command to the contralateral hand through the crossed corticospinal tract (CST). Mutations in NETRIN-1 alter motor control lateralization, leading to congenital mirror movements. To address the role of midline Netrin-1 on CST development and subsequent motor control, we analyzed the morphological and functional consequences of floor-plate Netrin-1 depletion in conditional knock-out mice (Shh::cre;Ntn1lox/lox mice).Here, we show that depletion of floor plate Netrin-1 critically disrupts midline crossing of the CST, whereas the other commissural systems are mostly preserved. The CST defect results in abnormal but functional ipsilateral projections, and is associated with abnormal symmetric movements. Therefore, our study reveals a new role for Netrin-1 in CST development. It also describes a unique mouse model recapitulating characteristics of human congenital mirror movements, through abnormal CST decussation.

scholarly journals SlitC-PlexinA1 mediates iterative inhibition for orderly passage of spinal commissural axons through the floor plate

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Hugo Ducuing ◽  
Thibault Gardette ◽  
Aurora Pignata ◽  
Karine Kindbeiter ◽  
Muriel Bozon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Chicken Embryo ◽  
Ex Vivo ◽  
Growth Cones ◽  
Floor Plate ◽  
Commissural Axons ◽  
Fluorescent Reporters ◽  
Midline Crossing ◽  
Repulsive Forces ◽  
Complex Architecture

Spinal commissural axon navigation across the midline in the floor plate requires repulsive forces from local Slit repellents. The long-held view is that Slits push growth cones forward and prevent them from turning back once they became sensitized to these cues after midline crossing. We analyzed with fluorescent reporters Slits distribution and FP glia morphology. We observed clusters of Slit-N and Slit-C fragments decorating a complex architecture of glial basal process ramifications. We found that PC2 proprotein convertase activity contributes to this pattern of ligands. Next, we studied Slit-C acting via PlexinA1 receptor shared with another FP repellent, the Semaphorin3B, through generation of a mouse model baring PlexinA1Y1815F mutation abrogating SlitC but not Sema3B responsiveness, manipulations in the chicken embryo, and ex vivo live imaging. This revealed a guidance mechanism by which SlitC constantly limits growth cone exploration, imposing ordered and forward-directed progression through aligned corridors formed by FP basal ramifications.

scholarly journals Sonic Hedgehog switches on Wnt/planar cell polarity signaling in commissural axon growth cones by reducing levels of Shisa2

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Keisuke Onishi ◽  
Yimin Zou
Keyword(s):  
Cell Polarity ◽  
Sonic Hedgehog ◽  
Planar Cell Polarity ◽  
Axon Growth ◽  
Growth Cones ◽  
Floor Plate ◽  
Commissural Axon ◽  
Commissural Axons ◽  
Midline Crossing ◽  
Regulatory Link

Commissural axons switch on responsiveness to Wnt attraction during midline crossing and turn anteriorly only after exiting the floor plate. We report here that Sonic Hedgehog (Shh)-Smoothened signaling downregulates Shisa2, which inhibits the glycosylation and cell surface presentation of Frizzled3 in rodent commissural axon growth cones. Constitutive Shisa2 expression causes randomized turning of post-crossing commissural axons along the anterior–posterior (A–P) axis. Loss of Shisa2 led to precocious anterior turning of commissural axons before or during midline crossing. Post-crossing commissural axon turning is completely randomized along the A–P axis when Wntless, which is essential for Wnt secretion, is conditionally knocked out in the floor plate. This regulatory link between Shh and planar cell polarity (PCP) signaling may also occur in other developmental processes.

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

2020 ◽  
Author(s):  
Hugo Ducuing ◽  
Thibault Gardette ◽  
Aurora Pignata ◽  
Karine Kindbeiter ◽  
Muriel Bozon ◽  
...  
Keyword(s):  
Growth Cone ◽  
Time Lapse ◽  
Floor Plate ◽  
Commissural Axons ◽  
Fluorescent Reporters ◽  
Midline Crossing ◽  
Navigation Path ◽  
A1 Receptor ◽  
Increasing Risk

SummarySensitization 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.

scholarly journals Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing

2015 ◽  
Vol 29 (24) ◽  
pp. 2617-2632
Author(s):  
Berenice Hernandez-Enriquez ◽  
Zhuhao Wu ◽  
Edward Martinez ◽  
Olav Olsen ◽  
Zaven Kaprielian ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Floor Plate ◽  
Axon Pathfinding ◽  
Developmentally Regulated ◽  
Commissural Axon ◽  
Commissural Axons ◽  
Receptor Complexes ◽  
Midline Crossing

Commissural axon guidance depends on a myriad of cues expressed by intermediate targets. Secreted semaphorins signal through neuropilin-2/plexin-A1 receptor complexes on post-crossing commissural axons to mediate floor plate repulsion in the mouse spinal cord. Here, we show that neuropilin-2/plexin-A1 are also coexpressed on commissural axons prior to midline crossing and can mediate precrossing semaphorin-induced repulsion in vitro. How premature semaphorin-induced repulsion of precrossing axons is suppressed in vivo is not known. We discovered that a novel source of floor plate-derived, but not axon-derived, neuropilin-2 is required for precrossing axon pathfinding. Floor plate-specific deletion of neuropilin-2 significantly reduces the presence of precrossing axons in the ventral spinal cord, which can be rescued by inhibiting plexin-A1 signaling in vivo. Our results show that floor plate-derived neuropilin-2 is developmentally regulated, functioning as a molecular sink to sequester semaphorins, preventing premature repulsion of precrossing axons prior to subsequent down-regulation, and allowing for semaphorin-mediated repulsion of post-crossing axons.

Shall I Move My Right or My Left Hand?

2003 ◽  
Vol 17 (2) ◽  
pp. 69-86 ◽  
Author(s):  
Claudio Babiloni ◽  
Fabio Babiloni ◽  
Filippo Carducci ◽  
Febo Cincotti ◽  
Claudio Del Percio ◽  
...  
Keyword(s):  
Bimanual Coordination ◽  
Central Area ◽  
Eeg Analysis ◽  
Complementary Information ◽  
Left Hand ◽  
Mirror Movements ◽  
Related Potentials ◽  
Motor Acts ◽  
Abstract Event

Abstract Event-related desynchronization/synchronization (ERD/ERS) at alpha (10Hz), beta (20Hz), and gamma (40Hz) bands and movement-related potentials (MRPs) were investigated in right-handed subjects who were “free” to decide the side of unilateral finger movements (“fixed” side as a control). As a novelty, this “multi-modal” EEG analysis was combined with the evaluation of involuntary mirror movements, taken as an index of “bimanual competition.” A main issue was whether the decision regarding the hand to be moved (“free” movements) could modulate ERD/ERS or MRPs overlying sensorimotor cortical areas typically involved in bimanual tasks. Compared to “fixed” movements, “free” movements induced the following effects: (1) more involuntary mirror movements discarded from EEG analysis; (2) stronger vertex MRPs (right motor acts); (3) a positive correlation between these potentials and the number of involuntary mirror movements; (4) gamma ERS over central areas; and (5) preponderance of postmovement beta ERS over left central area (dominant hemisphere). These results suggest that ERD/ERS and MRPs provide complementary information on the cortical processes belonging to a lateralized motor act. In this context, the results on vertex MRPs would indicate a key role of supplementary/cingulate motor areas not only for bimanual coordination but also for the control of “bimanual competition” and involuntary mirror movements.

Congenital mirror movements in a family with a novel mutation in the DCC gene

2011 ◽  
Vol 42 (S 01) ◽  
Author(s):  
GC Korenke ◽  
M Wagner ◽  
A Maak ◽  
G Rosenberger ◽  
K Kutsche
Keyword(s):  
Novel Mutation ◽  
Mirror Movements ◽  
Dcc Gene
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