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Heterophilic binding of L1 on unmyelinated sensory axons mediates Schwann cell adhesion and is required for axonal survival.

Haney CA, Sahenk Z, Li C, Lemmon VP, Roder J, Trapp BD - J. Cell Biol. (1999)

Bottom Line: We demonstrate that L1 is present on axons and Schwann cells of sensory unmyelinated fibers, but only on Schwann cells of sympathetic unmyelinated fibers.In L1-deficient sensory nerves, Schwann cells formed but failed to retain normal axonal ensheathment.In nerve transplant studies, loss of axonal-L1, but not Schwann cell-L1, reproduced the L1-deficient phenotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.

ABSTRACT
This study investigated the function of the adhesion molecule L1 in unmyelinated fibers of the peripheral nervous system (PNS) by analysis of L1- deficient mice. We demonstrate that L1 is present on axons and Schwann cells of sensory unmyelinated fibers, but only on Schwann cells of sympathetic unmyelinated fibers. In L1-deficient sensory nerves, Schwann cells formed but failed to retain normal axonal ensheathment. L1-deficient mice had reduced sensory function and loss of unmyelinated axons, while sympathetic unmyelinated axons appeared normal. In nerve transplant studies, loss of axonal-L1, but not Schwann cell-L1, reproduced the L1-deficient phenotype. These data establish that heterophilic axonal-L1 interactions mediate adhesion between unmyelinated sensory axons and Schwann cells, stabilize the polarization of Schwann cell surface membranes, and mediate a trophic effect that assures axonal survival.

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Nonmyelinating Schwann cells fail to maintain ensheathment of P60 L1-deficient sensory axons. In electron micrographs of wild-type (A) dorsal roots, most unmyelinated axons were surrounded by Schwann cells (A, arrowheads). In L1-deficient dorsal roots (B and D) many unmyelinated axons were not surrounded by Schwann cell processes (B and D, arrows), although some were partially surrounded by a basal lamina (C, double arrows). L1-deficient nonmyelinating Schwann cell processes often came into contact but did not ensheathe (D, arrowheads) small diameter axons. Some axons showed signs of degeneration (D, asterisk). Similar abnormalities were present in nonmyelinated fibers in MAG/L1-deficient dorsal root (C). Ax, Axon; Nu, Nucleus. Bars, 1 μm.
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Figure 2: Nonmyelinating Schwann cells fail to maintain ensheathment of P60 L1-deficient sensory axons. In electron micrographs of wild-type (A) dorsal roots, most unmyelinated axons were surrounded by Schwann cells (A, arrowheads). In L1-deficient dorsal roots (B and D) many unmyelinated axons were not surrounded by Schwann cell processes (B and D, arrows), although some were partially surrounded by a basal lamina (C, double arrows). L1-deficient nonmyelinating Schwann cell processes often came into contact but did not ensheathe (D, arrowheads) small diameter axons. Some axons showed signs of degeneration (D, asterisk). Similar abnormalities were present in nonmyelinated fibers in MAG/L1-deficient dorsal root (C). Ax, Axon; Nu, Nucleus. Bars, 1 μm.

Mentions: The ultrastructural appearance of unmyelinated fibers was compared in the sciatic nerve and dorsal roots of P60 L1-deficient and wild-type mice. As previously described (Peters et al. 1991), nonmyelinating Schwann cells in wild-type sciatic nerve ensheathed individual axons in separate cytoplasmic troughs (data not shown). In P60 dorsal roots from wild-type mice, many unmyelinated axons still remained in polyaxonal Schwann cell pockets (Fig. 2 A, arrowheads). Unmyelinated fibers in MAG-deficient dorsal roots had a similar ultrastructure as the unmyelinated fibers in wild-type dorsal root (data not shown). In L1-deficient dorsal roots examined at P60, many unmyelinated axons were not surrounded or were partially surrounded by Schwann cell processes. Unensheathed axons often contained fragments of basal lamina on their surface (Fig. 2, B–D, arrows) indicating former Schwann cell ensheathment. Evidence of ongoing axonal degeneration including axonal swelling, dissociation of microtubules and neurofilaments, and clumping of axonal contents (Dyck and Hopkins 1972) was apparent in the L1-deficient peripheral nerves (Fig. 2 D, asterisk). Small diameter axons without Schwann cells often abutted the basal lamina of myelinated fibers, and nonmyelinating Schwann cells extended processes passing near but not surrounding many naked axons (Fig. 2 D, arrowheads). The basal lamina was often discontinuous on the surface of these L1-deficient nonmyelinating Schwann cell processes. Lateral adhesion between adjacent Schwann cells of unmyelinated fibers was also disrupted (data not shown). Similar phenotypes were also present in sciatic and sural nerves of L1 and L1/MAG-deficient mice. Myelinated fibers in the L1-deficient mouse appeared similar to those in wild-type mice. Myelin membranes were tightly compacted and the periaxonal space was appropriately maintained at 12–14 nm. Myelination proceeded normally in the L1/MAG-deficient mice and fibers analyzed at P60 showed MAG-deficient phenotypes (Yin et al. 1998) in the myelinated fibers and the L1-deficient phenotypes in the unmyelinated fibers.


Heterophilic binding of L1 on unmyelinated sensory axons mediates Schwann cell adhesion and is required for axonal survival.

Haney CA, Sahenk Z, Li C, Lemmon VP, Roder J, Trapp BD - J. Cell Biol. (1999)

Nonmyelinating Schwann cells fail to maintain ensheathment of P60 L1-deficient sensory axons. In electron micrographs of wild-type (A) dorsal roots, most unmyelinated axons were surrounded by Schwann cells (A, arrowheads). In L1-deficient dorsal roots (B and D) many unmyelinated axons were not surrounded by Schwann cell processes (B and D, arrows), although some were partially surrounded by a basal lamina (C, double arrows). L1-deficient nonmyelinating Schwann cell processes often came into contact but did not ensheathe (D, arrowheads) small diameter axons. Some axons showed signs of degeneration (D, asterisk). Similar abnormalities were present in nonmyelinated fibers in MAG/L1-deficient dorsal root (C). Ax, Axon; Nu, Nucleus. Bars, 1 μm.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2169489&req=5

Figure 2: Nonmyelinating Schwann cells fail to maintain ensheathment of P60 L1-deficient sensory axons. In electron micrographs of wild-type (A) dorsal roots, most unmyelinated axons were surrounded by Schwann cells (A, arrowheads). In L1-deficient dorsal roots (B and D) many unmyelinated axons were not surrounded by Schwann cell processes (B and D, arrows), although some were partially surrounded by a basal lamina (C, double arrows). L1-deficient nonmyelinating Schwann cell processes often came into contact but did not ensheathe (D, arrowheads) small diameter axons. Some axons showed signs of degeneration (D, asterisk). Similar abnormalities were present in nonmyelinated fibers in MAG/L1-deficient dorsal root (C). Ax, Axon; Nu, Nucleus. Bars, 1 μm.
Mentions: The ultrastructural appearance of unmyelinated fibers was compared in the sciatic nerve and dorsal roots of P60 L1-deficient and wild-type mice. As previously described (Peters et al. 1991), nonmyelinating Schwann cells in wild-type sciatic nerve ensheathed individual axons in separate cytoplasmic troughs (data not shown). In P60 dorsal roots from wild-type mice, many unmyelinated axons still remained in polyaxonal Schwann cell pockets (Fig. 2 A, arrowheads). Unmyelinated fibers in MAG-deficient dorsal roots had a similar ultrastructure as the unmyelinated fibers in wild-type dorsal root (data not shown). In L1-deficient dorsal roots examined at P60, many unmyelinated axons were not surrounded or were partially surrounded by Schwann cell processes. Unensheathed axons often contained fragments of basal lamina on their surface (Fig. 2, B–D, arrows) indicating former Schwann cell ensheathment. Evidence of ongoing axonal degeneration including axonal swelling, dissociation of microtubules and neurofilaments, and clumping of axonal contents (Dyck and Hopkins 1972) was apparent in the L1-deficient peripheral nerves (Fig. 2 D, asterisk). Small diameter axons without Schwann cells often abutted the basal lamina of myelinated fibers, and nonmyelinating Schwann cells extended processes passing near but not surrounding many naked axons (Fig. 2 D, arrowheads). The basal lamina was often discontinuous on the surface of these L1-deficient nonmyelinating Schwann cell processes. Lateral adhesion between adjacent Schwann cells of unmyelinated fibers was also disrupted (data not shown). Similar phenotypes were also present in sciatic and sural nerves of L1 and L1/MAG-deficient mice. Myelinated fibers in the L1-deficient mouse appeared similar to those in wild-type mice. Myelin membranes were tightly compacted and the periaxonal space was appropriately maintained at 12–14 nm. Myelination proceeded normally in the L1/MAG-deficient mice and fibers analyzed at P60 showed MAG-deficient phenotypes (Yin et al. 1998) in the myelinated fibers and the L1-deficient phenotypes in the unmyelinated fibers.

Bottom Line: We demonstrate that L1 is present on axons and Schwann cells of sensory unmyelinated fibers, but only on Schwann cells of sympathetic unmyelinated fibers.In L1-deficient sensory nerves, Schwann cells formed but failed to retain normal axonal ensheathment.In nerve transplant studies, loss of axonal-L1, but not Schwann cell-L1, reproduced the L1-deficient phenotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.

ABSTRACT
This study investigated the function of the adhesion molecule L1 in unmyelinated fibers of the peripheral nervous system (PNS) by analysis of L1- deficient mice. We demonstrate that L1 is present on axons and Schwann cells of sensory unmyelinated fibers, but only on Schwann cells of sympathetic unmyelinated fibers. In L1-deficient sensory nerves, Schwann cells formed but failed to retain normal axonal ensheathment. L1-deficient mice had reduced sensory function and loss of unmyelinated axons, while sympathetic unmyelinated axons appeared normal. In nerve transplant studies, loss of axonal-L1, but not Schwann cell-L1, reproduced the L1-deficient phenotype. These data establish that heterophilic axonal-L1 interactions mediate adhesion between unmyelinated sensory axons and Schwann cells, stabilize the polarization of Schwann cell surface membranes, and mediate a trophic effect that assures axonal survival.

Show MeSH
Related in: MedlinePlus