Towards an understanding of semaphorin signalling in the spinal cord

O'Malley, Aisling; Shanley, Daniel K.; Kelly, Albert; Barry, Denis

doi:10.1016/j.gene.2014.10.005

Cited by 11 publications

(6 citation statements)

References 63 publications

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“…Our study provides evidence that semaphorin is an epidermis-derived ligand that instructs spatial patterning of sensory dendrites in Drosophila . In mammals, many members of the semaphorin family are expressed in sensory neurons, including those in dorsal root ganglia (Pasterkamp, 2012; O’Malley et al, 2014). It will be of great interest to determine whether epidermis-derived semaphorin also regulates morphogenesis of mammalian sensory neurons.…”

Section: Discussionmentioning

confidence: 99%

Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons

Meltzer

Yadav

Lee

et al. 2016

Neuron

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Summary Precise patterning of dendritic arbors is critical for the wiring and function of neural circuits. Dendrite-extracellular matrix (ECM) adhesion ensures that the dendrites of Drosophila dendritic arborization (da) sensory neurons are properly restricted in a 2D space, and thereby facilitates contact-mediated dendritic self-avoidance and tiling. However, the mechanisms regulating dendrite-ECM adhesion in vivo are poorly understood. Here, we show that mutations in the semaphorin ligand sema-2b lead to a dramatic increase in self-crossing of dendrites due to defects in dendrite-ECM adhesion, resulting in a failure to confine dendrites to a 2D plane. Furthermore, we find that Sema-2b is secreted from the epidermis and signals through the Plexin B receptor in neighboring neurons. Importantly, we find that Sema-2b/PlexB genetically and physically interacts with TORC2 complex, Tricornered (Trc) kinase and integrins. These results reveal a novel role for semaphorins in dendrite patterning and illustrate how epidermal-derived cues regulate neural circuit assembly.

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Section: Discussionmentioning

confidence: 99%

Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons

Meltzer

Yadav

Lee

et al. 2016

Neuron

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“…The neural tube, which will become the spinal cord, transforms drastically as interneurons are born and specified (Lai et al, 2016). The process by which sensory axons target specific spinal cord subregions has been studied in detail and is the subject of several reviews (Gardiner, 2011;Masuda et al, 2009;O'Malley et al, 2014;Olson et al, 2016). Although the molecular and cellular mechanisms that mediate innervation of peripheral target tissues are less well-understood, recent parallel investigations of skin biology and somatosensory neurons have begun to reveal how skin microdomains and touch receptors develop in unison.…”

Section: The Innervation Of Skin By Mechanoreceptorsmentioning

confidence: 99%

Developing a sense of touch

Jenkins

Lumpkin

2017

Development

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The sensation of touch is mediated by mechanosensory neurons that are embedded in skin and relay signals from the periphery to the central nervous system. During embryogenesis, axons elongate from these neurons to make contact with the developing skin. Concurrently, the epithelium of skin transforms from a homogeneous tissue into a heterogeneous organ that is made up of distinct layers and microdomains. Throughout this process, each neuronal terminal must form connections with an appropriate skin region to serve its function. This Review presents current knowledge of the development of the sensory microdomains in mammalian skin and the mechanosensory neurons that innervate them.

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“…Vertebrate semaphorins fall into 5 classes: class 3 semaphorins (Sema3) are secreted and signal through a neuropilin/plexin complex, while classes 4-7 (Sema4-7) are membrane associated and can bind plexin receptors directly, as can secreted Sema3E [27,28]. Semaphorins generally act as repulsive guidance molecules, though they can also mediate attraction, depending upon the receptor complex activated, which, in turn, can be neuronal subtype specific or timing dependent [29].…”

Section: Semaphorinsmentioning

confidence: 99%

“…Semaphorins prevent inappropriate monosynaptic connections between primary sensory neurons of the peripheral nervous system (PNS) and motor neurons in the spinal cord [30], and control projections at the CNS-PNS interface (Fig. 1) [27]. Large-diameter proprioceptive neurons that form the fibers of the ascending dorsal funiculus are prevented from aberrantly infiltrating the dorsal horn termination zone of cutaneous afferents by transmembrane semaphorin (Sema6C and Sema6D) signaling through PlexinA1 [31].…”

Section: Semaphorinsmentioning

confidence: 99%

Axon Guidance Molecules and Neural Circuit Remodeling After Spinal Cord Injury

Hollis

2016

Neurotherapeutics

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…once the development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. Santiago Ramón y CajalCajal's neurotropic theory postulates that the complexity of the nervous system arises from the collaboration of neurotropic signals from neuronal and non-neuronal cells and that once development has ended, a paucity of neurotropic signals means that the pathways of the central nervous system are Bfixed, ended, immutable^. While the capacity for regeneration and plasticity of the central nervous system may not be quite as paltry as Cajal proposed, regeneration is severely limited in scope as there is no spontaneous regeneration of long-distance projections in mammals and therefore limited opportunity for functional recovery following spinal cord injury. It is not a far stretch from Cajal to hypothesize that reappropriation of the neurotropic programs of development may be an appropriate strategy for reconstitution of injured circuits. It has become clear, however, that a significant number of the molecular cues governing circuit development become re-active after injury and many assume roles that paradoxically obstruct the functional re-wiring of severed neural connections. Therefore, the problem to address is how individual neural circuits respond to specific molecular cues following injury, and what strategies will be necessary for instigating functional repair or remodeling of the injured spinal cord.

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Towards an understanding of semaphorin signalling in the spinal cord

Cited by 11 publications

References 63 publications

Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons

Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons

Developing a sense of touch

Axon Guidance Molecules and Neural Circuit Remodeling After Spinal Cord Injury

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