Afadin Signaling at the Spinal Neuroepithelium Regulates Central Canal Formation and Gait Selection

Skarlatou, Sophie; Hérent, Coralie; Toscano, Elisa; Mendes, César S.; Bouvier, Julien; Zampieri, Niccolò

doi:10.1016/j.celrep.2020.107741

Cited by 15 publications

(34 citation statements)

References 63 publications

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“…We observed substantial differences in the densities and laminar distributions of commissural pre-MNs (cpre-MNs) at lumbar versus brachial levels ( (Table S1). The chick brachial-specific pre-MNs are thus comparable to the ectopic cpre-MNs in hop mutants in location, wiring and excitatory phenotype (14,43).…”

Section: Connectivity Of Pre-mns In the Chick Spinal Cordmentioning

confidence: 75%

Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds

Haimson

Meir

Sudakevitz-Merzbach

et al. 2021

Preprint

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Flight in birds evolved through patterning of the wings from forelimbs and transition from alternating gait to synchronous flapping. In mammals, the spinal midline guidance molecule ephrin-B3 instructs the wiring that enables limb alternation, and its deletion leads to synchronous hopping gait. Here we show that the ephrin-B3 protein in birds lacks several motifs present in other vertebrates, diminishing its affinity for the EphA4 receptor. The avian ephrin-B3 gene lacks an enhancer that drives midline expression, and is missing in Galliformes. The morphology and wiring at brachial levels of the chick spinal cord resemble those of ephrin-B3 null mice. Importantly, dorsal midline decussation, evident in the mutant mouse, is apparent at the chick brachial level, and is prevented by expression of exogenous ephrin-B3 at the roof plate. Our findings support a role for loss of ephrin-B3 function in shaping the avian brachial spinal cord circuitry and facilitating synchronous wing flapping.TeaserWalking vs flying: Deciphering the organization and evolution of the neuronal network that controls wing flapping in birds.

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Section: Connectivity Of Pre-mns In the Chick Spinal Cordmentioning

confidence: 75%

Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds

Haimson

Meir

Sudakevitz-Merzbach

et al. 2021

Preprint

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“…The mechanisms by which the frequency set point is achieved, and those allowing transiting from it will need to be investigated. A bulk of evidence indicates that transitions from walk, to trot and gallop are controlled by specific circuits in the brainstem centers for locomotor initiation (Bachmann et al, 2013;Caggiano et al, 2018;Josset et al, 2018) and in the executive centers of the spinal cord (Andersson et al, 2012;Talpalar et al, 2013;Bellardita and Kiehn, 2015;Skarlatou et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Immediate concerns would be to identify candidate trigger neurons, as well as respiratory frequency clamping mechanisms that need to be blind to the grade of trotting locomotor drives and labile upon gait transitioning. This should be achievable using selective interventional manipulations of locomotor and respiratory neuronal types, now both well-defined and accessible with molecular and genetic markers, viral tracers, and dedicated transgenic mice lines (Bouvier et al, 2010;Talpalar et al, 2013;Ruffault et al, 2015;Kiehn, 2016;Del Negro et al, 2018;Skarlatou et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Independent respiratory and locomotor rhythms in running mice

Hérent

Diem

Fortin

et al. 2020

Preprint

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Examining whether and how the rhythms of limb and breathing movements interact is highly informative about the mechanistic origin of hyperpnoea to exercise. However, studies have failed to reveal regularities. In particular, whether breathing frequency is inherently proportional to limb velocity and/or imposed by a synchronization of breaths to strides is still unclear. Here, we examined the specifications of respiratory changes during running in mice, the premier model for investigating, in a standardized manner, complex integrative tasks including adaptive breathing. We show that respiratory rate increases during running to a fixed and stable value, irrespective of trotting velocities and of inclination. Yet, respiratory rate was further enhanced during gallop. We also demonstrate the absence of temporal coordination of breaths to strides at any speed, intensity or gait. Our work thus highlights a hardwired mechanism that sets respiratory frequency independently of limb movements but in relation with the engaged locomotor program.

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“…Homozygous ChAT∷Cre mice (Rossi et al, 2011, Jackson lab, stock #006410) or heterozygous Olig2∷Cre mice (Dessaud et al, 2007) were crossed with homozygous RФGT mice (Jackson Lab, stock #024708), to generate ChAT∷Cre +/−; RФGT +/− or Olig2∷Cre +/−; RФGT +/− mice (Takatoh et al, 2013; Skarlatou et al, 2020) that were used for rabies tracing experiments. For experiments aimed at distinguishing excitatory and inhibitory populations of premotor interneurons, we crossed homozygous ChAT∷Cre mice with heterozygous GlyT2-EGFP mice (a gift from Prof. Zeilhofer, University of Zurich, Zeilhofer et al, 2005) and their double-positive offspring were mated with the homozygous RФGT mice.…”

Section: Methodsmentioning

confidence: 99%

“…For the experiments performed at MDC, spinal cords were processed as previously described (Skarlatou et al, 2020). Briefly, animals were anesthetized by intraperitoneal injection of ketamine /xylazine mix and transcardially perfused with ice-cold PBS until the liver was cleared of blood and followed by freshly made ice-cold 4% PFA.…”

Section: Methodsmentioning

confidence: 99%

Spinal premotor interneurons controlling antagonistic muscles are spatially intermingled

Ronzano

Skarlatou

Bannatyne

et al. 2021

Preprint

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The activity of flexor and extensor motor neurons is tightly regulated by a network of interneurons in the spinal cord. The introduction of rabies retrograde monosynaptic tracing has provided a powerful method to map interneurons directly connected to motor neurons so as to visualize premotor circuits. Previous strategies have used AAV for complementing rabies glycoprotein expression in motor neurons to obtain selectivity in transsynaptic transfer to identify premotor interneurons innervating specific motor neuron pools These studies revealed differences in the location of flexor and extensor premotor interneurons. Here, we report that by using a genetic approach to complement rabies glycoprotein expression in motor neurons, we did not observe any differences in the distribution of flexor and extensor premotor interneurons. In order to identify possible causes for these paradoxical findings, we discuss advantages and caveats of the experimental designs and suggest ways forward to resolve possible ambiguities. Furthermore, to obtain a complete picture of existing approaches and results we ask for contributions from the scientific community describing the use of additional mouse models, viral constructs, and complementation methods. The aim is to generate an open, comprehensive database to understand the specific organisation of premotor circuits.

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Afadin Signaling at the Spinal Neuroepithelium Regulates Central Canal Formation and Gait Selection

Abstract: Highlights d Afadin elimination from motor neuron progenitors causes hopping phenotype d Afadin function at the neuroepithelium controls organization of spinal midline d Miswiring of dI4-5, V0, and V2a premotor interneurons in afadin mutant mice

Cited by 15 publications

References 63 publications

Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds

Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds

Independent respiratory and locomotor rhythms in running mice

Spinal premotor interneurons controlling antagonistic muscles are spatially intermingled

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