Roles of axon guidance molecules in neuronal wiring in the developing spinal cord

Chédotal, Alain

doi:10.1038/s41583-019-0168-7

Cited by 112 publications

(96 citation statements)

References 236 publications

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“…Most neuro-epithelial calcium transients occur ventrally in the vicinity of the floor plate, a specialized neuro-epithelial structure located at the midline and spanning the entire length of the spinal cord 4,21 . The floor plate is named after the embryologist and anatomist Wilhelm His, Sr. who first identified it in 1888 21 and has since been shown to act as a major organizer for the formation of spinal motor network through the release of the morphogen Sonic Hedgehog, Shh 22 , and the axon guidance molecules Slit and Netrins 23 . Although the floor plate plays a central role during spinal cord development, its physiological properties remain poorly characterized.…”

Section: Main Textmentioning

confidence: 99%

Neuroepithelial progenitors generate and propagate non-neuronal action potentials across the spinal cord

Arulkandarajah

Osterstock

Lafont

et al. 2020

Preprint

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In the developing central nervous system of vertebrates, the emergence of electrical signals is thought to result exclusively from the differentiation of neurons 1-3 . Accordingly, the neuro-epithelial progenitors generating neurons and glial cells have been assumed to remain electrically passive. Here, we show that the floor plate of His -a neuro-epithelial organizer located at the ventral midline of the fetal spinal cord 4 -has the unexpected ability to generate large biphasic action potentials resulting from the combined activity of voltage-gated T-type calcium channels and sodium channels. Floor plate action potentials are recurrently triggered by the neurotransmitter acetylcholine released from cholinergic motor neurons during early episodes of spontaneous neural activity. Moreover, we found that floor plate cells are connected by gap junctions, form a functional syncytium with other neuro-epithelial progenitor domains and establish a ventral to dorsal depolarization gradient in the neuroepithelium. Finally, we show that floor plate action potentials are associated with calcium waves and propagate through gap junctions along the length of the fetal spinal cord. Our present work demonstrates that the floor plate of His acts as a unique neuro-epithelial electrical conduction system, sharing functional similarities with the myo-epithelial electrical conduction system of the heart known as the bundle of His 5 . This discovery profoundly change how we conceive the development, origin, evolution and extent of electrical signals in the central nervous system of vertebrates.

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Section: Main Textmentioning

confidence: 99%

Neuroepithelial progenitors generate and propagate non-neuronal action potentials across the spinal cord

Arulkandarajah

Osterstock

Lafont

et al. 2020

Preprint

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“…Moreover the FP is a source of both growth‐promoting and growth‐repulsive cues for commissural axons, such as netrin‐1 and Slits (Chédotal ). In vertebrates, spinal commissural axons navigate first ventrally toward the floor plate (Fig.…”

Section: The Developing Nervous Systemmentioning

confidence: 99%

“…The post‐crossing commissural neurons are thus expelled from the midline, and also prevented from re‐crossing the FP. At later stages, they follow rostro‐caudal gradients of guidance cues, turning rostrally or caudally in the ventral or lateral funiculi (Gaudet and Fonken ; Ducuing et al ; Chédotal ).…”

Section: The Developing Nervous Systemmentioning

confidence: 99%

Construction and reconstruction of brain circuits: normal and pathological axon guidance

Roig‐Puiggros

Vigouroux

Beckman

et al. 2019

Journal of Neurochemistry

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Perception of our environment entirely depends on the close interaction between the central and peripheral nervous system. In order to communicate each other, both systems must develop in parallel and in coordination. During development, axonal projections from the CNS as well as the PNS must extend over large distances to reach their appropriate target cells. To do so, they read and follow a series of axon guidance molecules. Interestingly, while these molecules play critical roles in guiding developing axons, they have also been shown to be critical in other major neurodevelopmental processes, such as the migration of cortical progenitors. Currently, a major hurdle for brain repair after injury or neurodegeneration is the absence of axonal regeneration in the mammalian CNS. By contrasts, PNS axons can regenerate. Many hypotheses have been put forward to explain this paradox but recent studies suggest that hacking neurodevelopmental mechanisms may be the key to promote CNS regeneration. Here we provide a seminar report written by trainees attending the second Flagship school held in Alpbach, Austria in September 2018 organized by the International Society for Neurochemistry (ISN) together with the Journal of Neurochemistry (JCN). This advanced school has brought together leaders in the fields of neurodevelopment and regeneration in order to discuss major keystones and future challenges in these respective fields.

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“…To establish neuronal connectivity in the adult brain, neurons located far from their targets must extend an axon that navigates over long distances during embryonic development to reach the correct target tissue. Using simple models such as the axonal binary decision of crossing or not the midline in vertebrates or invertebrates, different families of secreted (Netrin, Slits) and membrane (Eph/ephrins) proteins were initially identified as axon guidance molecules (Chédotal, 2019;Herrera et al, 2019;Stoeckli, 2018). Later, the highly conserved proteins Wnts −originally described as key regulators of body axis patterning, cell fate specification, proliferation, cell migration and carcinogenesis− were found to be also involved in axon guidance and mediate both attractive and repulsive responses in different contexts.…”

Section: Introductionmentioning

confidence: 99%

Zic2 abrogates an alternative Wnt signaling pathway to convert axon attraction into repulsion

Herrera

2019

Preprint

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Roles of axon guidance molecules in neuronal wiring in the developing spinal cord

Cited by 112 publications

References 236 publications

Neuroepithelial progenitors generate and propagate non-neuronal action potentials across the spinal cord

Neuroepithelial progenitors generate and propagate non-neuronal action potentials across the spinal cord

Construction and reconstruction of brain circuits: normal and pathological axon guidance

Zic2 abrogates an alternative Wnt signaling pathway to convert axon attraction into repulsion

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