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Semaphorin6A acts as a gate keeper between the central and the peripheral nervous system.

Mauti O, Domanitskaya E, Andermatt I, Sadhu R, Stoeckli ET - Neural Dev (2007)

Bottom Line: Ablation of the boundary cap resulted in emigration of motoneurons from the ventral spinal cord along the ventral roots.Loss of either PlexinA4 or Sema6D function had an effect only at the dorsal root entry site but not at the ventral motor axon exit point.At the dorsal root entry site it organizes the segregation of dorsal roots.

View Article: PubMed Central - HTML - PubMed

Affiliation: Developmental Neuroscience, Institute of Zoology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Olivier.Mauti@zool.uzh.ch

ABSTRACT

Background: During spinal cord development, expression of chicken SEMAPHORIN6A (SEMA6A) is almost exclusively found in the boundary caps at the ventral motor axon exit point and at the dorsal root entry site. The boundary cap cells are derived from a population of late migrating neural crest cells. They form a transient structure at the transition zone between the peripheral nervous system (PNS) and the central nervous system (CNS). Ablation of the boundary cap resulted in emigration of motoneurons from the ventral spinal cord along the ventral roots. Based on its very restricted expression in boundary cap cells, we tested for a role of Sema6A as a gate keeper between the CNS and the PNS.

Results: Downregulation of Sema6A in boundary cap cells by in ovo RNA interference resulted in motoneurons streaming out of the spinal cord along the ventral roots, and in the failure of dorsal roots to form and segregate properly. PlexinAs interact with class 6 semaphorins and are expressed by both motoneurons and sensory neurons. Knockdown of PlexinA1 reproduced the phenotype seen after loss of Sema6A function both at the ventral motor exit point and at the dorsal root entry site of the lumbosacral spinal cord. Loss of either PlexinA4 or Sema6D function had an effect only at the dorsal root entry site but not at the ventral motor axon exit point.

Conclusion: Sema6A acts as a gate keeper between the PNS and the CNS both ventrally and dorsally. It is required for the clustering of boundary cap cells at the PNS/CNS interface and, thus, prevents motoneurons from streaming out of the ventral spinal cord. At the dorsal root entry site it organizes the segregation of dorsal roots.

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Sema6A acts as a gate keeper at the VMEP by triggering the formation of BCC clusters. Our results support a model that suggests a role for Sema6A in BCC cluster initiation. (a) Motor axons leaving the ventral spinal cord express PlexinA1 on their surface (yellow rectangle). Boundary cap cells (blue circles) express Sema6A (green rectangles), which recognizes PlexinA1 on motor axons, resulting in the accumulation of BCCs and, subsequently, in their clustering. By an unknown mechanism the BCC cluster prevents motor neurons (red circles) but not motor axons from translocating into the periphery. (b, c) Consistent with this model, the absence of PlexinA1 from motor axons would remove the stop signal (b) and the absence of Sema6A from BCCs would remove the receptor for the stop signal (c). In both cases, BCC clusters would fail to form properly and motoneurons would not be confined to the ventral spinal cord but migrate into the periphery along the ventral roots. The behavior of sensory axons at the dorsal BCC clusters is more complex and cannot be fully explained by this model.
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Figure 9: Sema6A acts as a gate keeper at the VMEP by triggering the formation of BCC clusters. Our results support a model that suggests a role for Sema6A in BCC cluster initiation. (a) Motor axons leaving the ventral spinal cord express PlexinA1 on their surface (yellow rectangle). Boundary cap cells (blue circles) express Sema6A (green rectangles), which recognizes PlexinA1 on motor axons, resulting in the accumulation of BCCs and, subsequently, in their clustering. By an unknown mechanism the BCC cluster prevents motor neurons (red circles) but not motor axons from translocating into the periphery. (b, c) Consistent with this model, the absence of PlexinA1 from motor axons would remove the stop signal (b) and the absence of Sema6A from BCCs would remove the receptor for the stop signal (c). In both cases, BCC clusters would fail to form properly and motoneurons would not be confined to the ventral spinal cord but migrate into the periphery along the ventral roots. The behavior of sensory axons at the dorsal BCC clusters is more complex and cannot be fully explained by this model.

Mentions: Based on our results, we propose a model where Sema6A in BCCs is required for them to home in on the entry and exit sites of the spinal cord, where they form the boundary cap (Figure 9). PlexinA1 on axons provides the stop signal that is recognized by Sema6A on migrating boundary cap cells. Because we were unable to detect a homophilic Sema6A interaction and none of the PlexinAs is expressed in BCCs, Sema6A is unlikely to be responsible for BCC clustering directly, that is, by mediating cell-cell contact between BCCs. Cadherin-7 is a good candidate for the adhesion molecule that might be responsible for the formation of tight cell-cell contacts between BCCs. Cadherin-7 is expressed strongly when BCCs have reached the aggregation site but not while they are still migrating, and it was shown to bind homophilically [47,56].


Semaphorin6A acts as a gate keeper between the central and the peripheral nervous system.

Mauti O, Domanitskaya E, Andermatt I, Sadhu R, Stoeckli ET - Neural Dev (2007)

Sema6A acts as a gate keeper at the VMEP by triggering the formation of BCC clusters. Our results support a model that suggests a role for Sema6A in BCC cluster initiation. (a) Motor axons leaving the ventral spinal cord express PlexinA1 on their surface (yellow rectangle). Boundary cap cells (blue circles) express Sema6A (green rectangles), which recognizes PlexinA1 on motor axons, resulting in the accumulation of BCCs and, subsequently, in their clustering. By an unknown mechanism the BCC cluster prevents motor neurons (red circles) but not motor axons from translocating into the periphery. (b, c) Consistent with this model, the absence of PlexinA1 from motor axons would remove the stop signal (b) and the absence of Sema6A from BCCs would remove the receptor for the stop signal (c). In both cases, BCC clusters would fail to form properly and motoneurons would not be confined to the ventral spinal cord but migrate into the periphery along the ventral roots. The behavior of sensory axons at the dorsal BCC clusters is more complex and cannot be fully explained by this model.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2238753&req=5

Figure 9: Sema6A acts as a gate keeper at the VMEP by triggering the formation of BCC clusters. Our results support a model that suggests a role for Sema6A in BCC cluster initiation. (a) Motor axons leaving the ventral spinal cord express PlexinA1 on their surface (yellow rectangle). Boundary cap cells (blue circles) express Sema6A (green rectangles), which recognizes PlexinA1 on motor axons, resulting in the accumulation of BCCs and, subsequently, in their clustering. By an unknown mechanism the BCC cluster prevents motor neurons (red circles) but not motor axons from translocating into the periphery. (b, c) Consistent with this model, the absence of PlexinA1 from motor axons would remove the stop signal (b) and the absence of Sema6A from BCCs would remove the receptor for the stop signal (c). In both cases, BCC clusters would fail to form properly and motoneurons would not be confined to the ventral spinal cord but migrate into the periphery along the ventral roots. The behavior of sensory axons at the dorsal BCC clusters is more complex and cannot be fully explained by this model.
Mentions: Based on our results, we propose a model where Sema6A in BCCs is required for them to home in on the entry and exit sites of the spinal cord, where they form the boundary cap (Figure 9). PlexinA1 on axons provides the stop signal that is recognized by Sema6A on migrating boundary cap cells. Because we were unable to detect a homophilic Sema6A interaction and none of the PlexinAs is expressed in BCCs, Sema6A is unlikely to be responsible for BCC clustering directly, that is, by mediating cell-cell contact between BCCs. Cadherin-7 is a good candidate for the adhesion molecule that might be responsible for the formation of tight cell-cell contacts between BCCs. Cadherin-7 is expressed strongly when BCCs have reached the aggregation site but not while they are still migrating, and it was shown to bind homophilically [47,56].

Bottom Line: Ablation of the boundary cap resulted in emigration of motoneurons from the ventral spinal cord along the ventral roots.Loss of either PlexinA4 or Sema6D function had an effect only at the dorsal root entry site but not at the ventral motor axon exit point.At the dorsal root entry site it organizes the segregation of dorsal roots.

View Article: PubMed Central - HTML - PubMed

Affiliation: Developmental Neuroscience, Institute of Zoology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Olivier.Mauti@zool.uzh.ch

ABSTRACT

Background: During spinal cord development, expression of chicken SEMAPHORIN6A (SEMA6A) is almost exclusively found in the boundary caps at the ventral motor axon exit point and at the dorsal root entry site. The boundary cap cells are derived from a population of late migrating neural crest cells. They form a transient structure at the transition zone between the peripheral nervous system (PNS) and the central nervous system (CNS). Ablation of the boundary cap resulted in emigration of motoneurons from the ventral spinal cord along the ventral roots. Based on its very restricted expression in boundary cap cells, we tested for a role of Sema6A as a gate keeper between the CNS and the PNS.

Results: Downregulation of Sema6A in boundary cap cells by in ovo RNA interference resulted in motoneurons streaming out of the spinal cord along the ventral roots, and in the failure of dorsal roots to form and segregate properly. PlexinAs interact with class 6 semaphorins and are expressed by both motoneurons and sensory neurons. Knockdown of PlexinA1 reproduced the phenotype seen after loss of Sema6A function both at the ventral motor exit point and at the dorsal root entry site of the lumbosacral spinal cord. Loss of either PlexinA4 or Sema6D function had an effect only at the dorsal root entry site but not at the ventral motor axon exit point.

Conclusion: Sema6A acts as a gate keeper between the PNS and the CNS both ventrally and dorsally. It is required for the clustering of boundary cap cells at the PNS/CNS interface and, thus, prevents motoneurons from streaming out of the ventral spinal cord. At the dorsal root entry site it organizes the segregation of dorsal roots.

Show MeSH
Related in: MedlinePlus