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.

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.

Commissural axon pathfinding on the contralateral side of the floor plate: a role for B-class ephrins in specifying the dorsoventral position of longitudinally projecting commissural axons

Development ◽  
2001 ◽  
Vol 128 (23) ◽  
pp. 4859-4871 ◽  
Author(s):  
Ralph Imondi ◽  
Zaven Kaprielian
Keyword(s):  
Spinal Cord ◽  
Late Phase ◽  
Longitudinal Axis ◽  
Contralateral Side ◽  
Floor Plate ◽  
Axon Pathfinding ◽  
Lower Vertebrate ◽  
Commissural Axon ◽  
Commissural Axons

In both invertebrate and lower vertebrate species, decussated commissural axons travel away from the midline and assume positions within distinct longitudinal tracts. We demonstrate that in the developing chick and mouse spinal cord, most dorsally situated commissural neuron populations extend axons across the ventral midline and through the ventral white matter along an arcuate trajectory on the contralateral side of the floor plate. Within the dorsal (chick) and intermediate (mouse) marginal zone, commissural axons turn at a conserved boundary of transmembrane ephrin expression, adjacent to which they form a discrete ascending fiber tract. In vitro perturbation of endogenous EphB-ephrinB interactions results in the failure of commissural axons to turn at the appropriate dorsoventral position on the contralateral side of the spinal cord; consequently, axons inappropriately invade more dorsal regions of B-class ephrin expression in the dorsal spinal cord. Taken together, these observations suggest that B-class ephrins act locally during a late phase of commissural axon pathfinding to specify the dorsoventral position at which decussated commissural axons turn into the longitudinal axis.

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.

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.

Characterization of hyperpolarization-activated currents in deep dorsal horn neurons of neonate mouse spinal cord in vitro

2013 ◽  
Vol 70 ◽  
pp. 148-155 ◽  
Author(s):  
Ivan Rivera-Arconada ◽  
Carolina Roza ◽  
Jose Antonio Lopez-Garcia
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Mouse Spinal Cord ◽  
Dorsal Horn Neurons

scholarly journals An in vitro functionally mature mouse spinal cord preparation for the study of spinal motor networks

1999 ◽  
Vol 816 (2) ◽  
pp. 493-499 ◽  
Author(s):  
Zhiyu Jiang ◽  
Kevin P Carlin ◽  
Robert M Brownstone
Keyword(s):  
Spinal Cord ◽  
Mouse Spinal Cord ◽  
Spinal Motor ◽  
Mature Mouse

scholarly journals Commisural axon pathfinding on the contralateral side of the ventral midline in the developing mouse spinal cord

2006 ◽  
Vol 295 (1) ◽  
pp. 339-340
Author(s):  
Zaven Kaprielian ◽  
Stephanie R. Kadison ◽  
Stacey L. Reeber ◽  
Jane E. Johnson ◽  
Fujio Murakami ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Contralateral Side ◽  
Axon Pathfinding ◽  
Ventral Midline ◽  
Mouse Spinal Cord

scholarly journals EPH/EPHRIN SIGNALING CONTROLS PROGENITOR IDENTITIES IN THE VENTRAL SPINAL CORD

2016 ◽  
Author(s):  
Julien Laussu ◽  
Christophe Audouard ◽  
Anthony Kischel ◽  
Poincyane Assis-Nascimento ◽  
Nathalie Escalas ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Sonic Hedgehog ◽  
Cell Communication ◽  
Dependent Manner ◽  
Eph Receptors ◽  
Loss Of Function ◽  
Summary Statement ◽  
Dose Dependent ◽  
Ventral Spinal Cord

SUMMARY STATEMENTThis article by Laussu et al. describes a role for Eph:ephrin signaling in controlling the identity of neural progenitors in the ventral spinal cord.Early specification of progenitors of the ventral spinal cord involves the morphogen Sonic Hedgehog which induces distinct progenitor identities in a dose-dependent manner. Following these initial patterning events, progenitor identities have to be maintained in order to generate appropriate numbers of progeny. Here we provide evidence that communication via Eph:ephrin signaling is required to maintain progenitor identities in the ventral spinal cord. We show that ephrinB2 and ephrinB3 are expressed in restricted progenitor domains in the ventral spinal cord while several Eph receptors are more broadly expressed. Further, we provide evidence that expression of Efnb3 and EphA4 is controlled by Shh. Genetic loss-of-function analyses indicate that expression of ephrinB2 and ephrinB3 is required to control progenitor identities and in vitro experiments reveal that activation of Eph forward signaling in spinal progenitors up-regulates the expression of the identity transcription factor Nkx2.2. Altogether our results indicate that cell-to-cell communication is necessary to control progenitor identity in the ventral spinal cord.

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