Ventral midline cells are required for the local control of commissural axon guidance in the mouse spinal cord

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3649-3659
Author(s):  
M.P. Matise ◽  
M. Lustig ◽  
T. Sakurai ◽  
M. Grumet ◽  
A.L. Joyner
Keyword(s):  
Spinal Cord ◽  
Critical Role ◽  
Floor Plate ◽  
Posterior Commissure ◽  
Ventral Midline ◽  
Mouse Spinal Cord ◽  
Commissural Axons ◽  
Midline Cells

Specialized cells at the midline of the central nervous system have been implicated in controlling axon projections in both invertebrates and vertebrates. To address the requirement for ventral midline cells in providing cues to commissural axons in mice, we have analyzed Gli2 mouse mutants, which lack specifically the floor plate and immediately adjacent interneurons. We show that a Dbx1 enhancer drives tau-lacZ expression in a subpopulation of commissural axons and, using a reporter line generated from this construct, as well as DiI tracing, we find that commissural axons projected to the ventral midline in Gli2(−/−) embryos. Netrin1 mRNA expression was detected in Gli2(−/−) embryos and, although much weaker than in wild-type embryos, was found in a dorsally decreasing gradient. This result demonstrates that while the floor plate can serve as a source of long-range cues for C-axons in vitro, it is not required in vivo for the guidance of commissural axons to the ventral midline in the mouse spinal cord. After reaching the ventral midline, most commissural axons remained clustered in Gli2(−/−) embryos, although some were able to extend longitudinally. Interestingly, some of the longitudinally projecting axons in Gli2(−/−) embryos extended caudally and others rostrally at the ventral midline, in contrast to normal embryos in which virtually all commissural axons turn rostrally after crossing the midline. This finding indicates a critical role for ventral midline cells in regulating the rostral polarity choice made by commissural axons after they cross the midline. In addition, we provide evidence that interactions between commissural axons and floor plate cells are required to modulate the localization of Nr-CAM and TAG-1 proteins on axons at the midline. Finally, we show that the floor plate is not required for the early trajectory of motoneurons or axons of the posterior commissure, whose projections are directed away from the ventral midline in both WT and Gli2(−/−) embryos, although they are less well organized in Gli2(−/−)mutants.

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.

scholarly journals Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-21 ◽  
Author(s):  
Elisa Garcia ◽  
Jorge Aguilar-Cevallos ◽  
Raul Silva-Garcia ◽  
Antonio Ibarra
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Critical Role ◽  
Glutamate Excitotoxicity ◽  
Signaling Proteins ◽  
Neurodegenerative Process ◽  
Cord Injury ◽  
Ion Imbalance

Spinal cord injury results in a life-disrupting series of deleterious interconnected mechanisms encompassed by the primary and secondary injury. These events are mediated by the upregulation of genes with roles in inflammation, transcription, and signaling proteins. In particular, cytokines and growth factors are signaling proteins that have important roles in the pathophysiology of SCI. The balance between the proinflammatory and anti-inflammatory effects of these molecules plays a critical role in the progression and outcome of the lesion. The excessive inflammatory Th1 and Th17 phenotypes observed after SCI tilt the scale towards a proinflammatory environment, which exacerbates the deleterious mechanisms present after the injury. These mechanisms include the disruption of the spinal cord blood barrier, edema and ion imbalance, in particular intracellular calcium and sodium concentrations, glutamate excitotoxicity, free radicals, and the inflammatory response contributing to the neurodegenerative process which is characterized by demyelination and apoptosis of neuronal tissue.

Complementary expression of transmembrane ephrins and their receptors in the mouse spinal cord: a possible role in constraining the orientation of longitudinally projecting axons

Development ◽  
2000 ◽  
Vol 127 (7) ◽  
pp. 1397-1410 ◽  
Author(s):  
R. Imondi ◽  
C. Wideman ◽  
Z. Kaprielian
Keyword(s):  
Spinal Cord ◽  
Floor Plate ◽  
Plate Boundaries ◽  
Eph Receptors ◽  
Axon Pathfinding ◽  
Mouse Spinal Cord ◽  
Commissural Axon ◽  
Ligand Interactions ◽  
Ventral Funiculus

In the developing spinal cord, axons project in both the transverse plane, perpendicular to the floor plate, and in the longitudinal plane, parallel to the floor plate. For many axons, the floor plate is a source of long- and short-range guidance cues that govern growth along both dimensions. We show here that B-class transmembrane ephrins and their receptors are reciprocally expressed on floor plate cells and longitudinally projecting axons in the mouse spinal cord. During the period of commissural axon pathfinding, B-class ephrin protein is expressed at the lateral floor plate boundaries, at the interface between the floor plate and the ventral funiculus. In contrast, B-class Eph receptors are expressed on decussated commissural axon segments projecting within the ventral funiculus, and on ipsilaterally projecting axons constituting the lateral funiculus. Soluble forms of all three B-class ephrins bind to, and induce the collapse of, commissural growth cones in vitro. The collapse-inducing activity associated with B-class ephrins is likely to be mediated by EphB1. Taken together, these data support a possible role for repulsive B-class Eph receptor/ligand interactions in constraining the orientation of longitudinal axon projections at the ventral midline.

Orientation of commissural axons in vitro in response to a floor plate-derived chemoattractant

Development ◽  
1990 ◽  
Vol 110 (1) ◽  
pp. 19-30 ◽  
Author(s):  
M. Placzek ◽  
M. Tessier-Lavigne ◽  
T. Jessell ◽  
J. Dodd
Keyword(s):  
Spinal Cord ◽  
Collagen Gel ◽  
Axon Growth ◽  
Local Environment ◽  
Floor Plate ◽  
Target Cells ◽  
Commissural Axon ◽  
Commissural Axons ◽  
Commissural Neurons

Developing axons are guided to their targets by molecular cues in their local environment. Some cues are short-range, deriving from cells along axonal pathways. There is also increasing evidence for longer-range guidance cues, in the form of gradients of diffusible chemoattractant molecules, which originate from restricted populations of target cells. The guidance of developing commissural axons within the spinal cord depends on one of their intermediate cellular targets, the floor plate. We have shown previously that floor plate cells secrete a diffusible factor(s) that can alter the direction of commissural axon growth in vitro. Here we show that the factor is an effective chemoattractant for commissural axons. It can diffuse considerable distances through a collagen gel matrix and through dorsal and ventral neural epithelium in vitro to reorient the growth of virtually all commissural axons. The orientation of axons occurs in the absence of detectable effects on the survival of commissural neurons or on the rate of commissural axon extension. The regionally restricted expression of the factor suggests that it is present in the embryonic spinal cord in a gradient with its high point at the floor plate. These observations support the idea that the guidance of commissural axons to the ventral midline of the spinal cord results in part from the secretion of a chemoattractant by the floor plate.

Degradation of nociceptin (orphanin FQ) by mouse spinal cord synaptic membranes is triggered by endopeptidase-24.11: an in vitro and in vivo study

2002 ◽  
Vol 64 (8) ◽  
pp. 1293-1303 ◽  
Author(s):  
Chikai Sakurada ◽  
Shinobu Sakurada ◽  
Tohru Orito ◽  
Koichi Tan-No ◽  
Tsukasa Sakurada
Keyword(s):  
Spinal Cord ◽  
In Vivo Study ◽  
Synaptic Membranes ◽  
Orphanin Fq ◽  
Mouse Spinal Cord ◽  
Endopeptidase 24.11

Moving From an Averaged to Specific View of Spinal Cord Pain Processing Circuits

2007 ◽  
Vol 98 (3) ◽  
pp. 1057-1063 ◽  
Author(s):  
B. A. Graham ◽  
A. M. Brichta ◽  
R. J. Callister
Keyword(s):  
Spinal Cord ◽  
Neuronal Excitability ◽  
Critical Role ◽  
Spinal Pain ◽  
Pain Processing ◽  
In Vivo Animal Models ◽  
Processing Mechanisms ◽  
Made In

Neurons in the superficial dorsal horn (SDH) of the spinal cord play a critical role in processing potentially painful or noxious signals from skin, muscle, and viscera. Many acute pain therapies are based on the notion that altering the excitability of SDH neurons can block or gate these signals and reduce pain. This same notion also underlies treatments for certain chronic pain states. Basic scientists are now beginning to identify a number of potential molecular targets for spinal cord–based pain therapies with a focus on ion channels and receptors that can alter neuronal excitability. The current challenge in pain research is to identify which are the most promising targets and how their manipulation alters pain processing. In this review, we propose that our understanding of spinal pain processing mechanisms and translation of these discoveries into pain therapies could be improved by 1) better appreciating and understanding neuronal heterogeneity in the SDH; 2) establishing connectivity patterns among SDH neuron types; and 3) testing and extending findings made in vitro to intact (in vivo) animal models. As this information becomes available, it will be possible to determine the precise distribution of potential therapeutic targets on various SDH neuron types within specific circuits known to be functionally important in spinal pain processing.

Bone morphogenetic proteins negatively control oligodendrocyte precursor specification in the chick spinal cord

Development ◽  
2002 ◽  
Vol 129 (22) ◽  
pp. 5117-5130 ◽  
Author(s):  
Soraya Mekki-Dauriac ◽  
Eric Agius ◽  
Paulette Kan ◽  
Philippe Cochard
Keyword(s):  
Spinal Cord ◽  
Bone Morphogenetic Proteins ◽  
Restricted Region ◽  
Oligodendrocyte Precursor ◽  
Bmp Signalling ◽  
Oligodendrocyte Development ◽  
Midline Cells ◽  
Chick Spinal Cord

In the vertebrate spinal cord, oligodendrocytes originate from a restricted region of the ventral neuroepithelium. This ventral localisation of oligodendrocyte precursors (OLPs) depends on the inductive influence of sonic hedgehog (Shh) secreted by ventral midline cells. We have investigated whether the ventral restriction of OLP specification might also depend on inhibiting signals mediated by bone morphogenetic proteins (BMPs). BMPs invariably and markedly inhibited oligodendrocyte development in ventral neural tissue both in vitro and in vivo. Conversely, in vivo ablation of the dorsal most part of the chick spinal cord or inactivation of BMP signalling using grafts of noggin-producing cells promoted the appearance of neuroepithelial OLPs dorsal to their normal domain of emergence, showing that endogenous BMPs contribute to the inhibition of oligodendrocyte development in the spinal cord. BMPs were able to oppose the Shh-mediated induction of OLPs in spinal cord neuroepithelial explants dissected before oligodendrocyte induction,suggesting that BMPs may repress OLP specification by interfering with Shh signalling in vivo. Strikingly, among the transcription factors involved in OLP specification, BMP treatment strongly inhibited the expression of Olig2 but not of Nkx2.2, suggesting that BMP-mediated inhibition of oligodendrogenesis is controlled through the repression of the former transcription factor. Altogether, our data show that oligodendrogenesis is not only regulated by ventral inductive signals such as Shh, but also by dorsal inhibiting signals including BMP factors. They suggest that the dorsoventral position of OLPs depends on a tightly regulated balance between Shh and BMP activities.

Nogo-B is the major form of Nogo at the floor plate and likely mediates crossing of commissural axons in the mouse spinal cord

2017 ◽  
Vol 525 (13) ◽  
pp. 2915-2928 ◽  
Author(s):  
Liqing Wang ◽  
Chao Yu ◽  
Jun Wang ◽  
Peggy Leung ◽  
Ding Ma ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Floor Plate ◽  
Mouse Spinal Cord ◽  
Commissural Axons ◽  
Major Form

Perturbation of neuronal differentiation and axon guidance in the spinal cord of mouse embryos lacking a floor plate: analysis of Danforth's short-tail mutation

Development ◽  
1991 ◽  
Vol 113 (2) ◽  
pp. 625-639 ◽  
Author(s):  
P. Bovolenta ◽  
J. Dodd
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Motor Neurons ◽  
Cell Types ◽  
Floor Plate ◽  
Ventral Midline ◽  
Cellular Targets ◽  
Commissural Axons ◽  
Short Tail ◽  
Plate Analysis

The floor plate of the vertebrate nervous system has been implicated in the guidance of commissural axons at the ventral midline. Experiments in chick have also suggested that at earlier stages of development the floor plate induces the differentiation of motor neurons and other neurons of the ventral spinal cord. Here we have examined the development of the spinal cord in a mouse mutant, Danforth's short-tail, in which the floor plate is absent from caudal regions of the neuraxis. In affected regions of the spinal cord, commissural axons exhibited aberrant projection patterns as they reached and crossed the ventral midline. In addition, motor neurons were absent or markedly reduced in number in regions of the spinal cord lacking a floor plate. Our results suggest that the floor plate is indeed an intermediate target in the projection of commissural axons and support the idea that several different mechanisms operate in concert in the guidance of axons to their cellular targets in the developing nervous system. In addition, these experiments suggest that the mechanisms that govern the differentiation of the floor plate and other ventral cell types in the neural tube are common to mammals and lower vertebrates.

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