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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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L1 is expressed by adult unmyelinated sensory but not sympathetic axons. In teased nerve fibers from P60 wild-type mouse dorsal root (A), L1 antibodies selectively stained unmyelinated fibers. L1 immunoreactivity surrounds the nucleus of a nonmyelinating Schwann cell (A, arrowhead) and confirms L1 expression by Schwann cells (A, arrows). L1 immunoreactivity in transverse cryosections of P60 wild-type nerve shows typical appearance of nonmyelinated fibers (B, arrows). Myelinated fibers (B, arrowheads) were not labeled with the L1 antibody. Sections (20 μm thick) from dorsal root ganglia (DRG) were double-labeled for L1 (C, red) and nonphosphorylated neurofilament (C, green). The plasma membrane (C, double arrowhead) and axon (C, arrowhead) of the small diameter neurons and the unmyelinated fibers (C, arrow) were L1-positive. Large diameter myelinated axons (C, asterisk) were labeled by neurofilament but not L1 antibodies. In sections (20 μm thick) of P60 DRG, small diameter neurons (D, arrows) were double-labeled for L1 (D, red) and Calcitonin gene-related product (CGRP) (D, green). The axons of these neurons were also L1-positive (D, arrowheads). In sections (20 μm thick) of P60 mouse superior cervical ganglia (SCG), neurons (E, arrowheads) and the axons exiting neuronal cell bodies were positive for neurofilament (green) but not for L1 (red). The nonmyelinating Schwann cells surrounding the SCG axons were L1-positive (E, arrow). Bars: (A) 30 μm; (B–D) 10 μm; (E) 25 μm.
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Figure 5: L1 is expressed by adult unmyelinated sensory but not sympathetic axons. In teased nerve fibers from P60 wild-type mouse dorsal root (A), L1 antibodies selectively stained unmyelinated fibers. L1 immunoreactivity surrounds the nucleus of a nonmyelinating Schwann cell (A, arrowhead) and confirms L1 expression by Schwann cells (A, arrows). L1 immunoreactivity in transverse cryosections of P60 wild-type nerve shows typical appearance of nonmyelinated fibers (B, arrows). Myelinated fibers (B, arrowheads) were not labeled with the L1 antibody. Sections (20 μm thick) from dorsal root ganglia (DRG) were double-labeled for L1 (C, red) and nonphosphorylated neurofilament (C, green). The plasma membrane (C, double arrowhead) and axon (C, arrowhead) of the small diameter neurons and the unmyelinated fibers (C, arrow) were L1-positive. Large diameter myelinated axons (C, asterisk) were labeled by neurofilament but not L1 antibodies. In sections (20 μm thick) of P60 DRG, small diameter neurons (D, arrows) were double-labeled for L1 (D, red) and Calcitonin gene-related product (CGRP) (D, green). The axons of these neurons were also L1-positive (D, arrowheads). In sections (20 μm thick) of P60 mouse superior cervical ganglia (SCG), neurons (E, arrowheads) and the axons exiting neuronal cell bodies were positive for neurofilament (green) but not for L1 (red). The nonmyelinating Schwann cells surrounding the SCG axons were L1-positive (E, arrow). Bars: (A) 30 μm; (B–D) 10 μm; (E) 25 μm.

Mentions: To investigate if the different phenotype in sensory and sympathetic unmyelinated fibers was due to differential expression of L1, the immunocytochemical localization of L1 was compared in dorsal roots and cervical sympathetic trunks from P60 wild-type mice. Unmyelinated fibers in teased fiber preparations from dorsal roots were positive for L1 (Fig. 5 A, arrows). L1 immunoprecipitate was clearly delineated in the nonmyelinating Schwann cells. In transverse one micron thick cryosections from P60 wild-type mouse sciatic nerve L1 antibodies also stained the Schwann cells of unmyelinated fibers (Fig. 5 B, arrows). However, the optical resolution of immunostaining in these preparations was insufficient to determine whether L1 was also present in the small diameter axons. Myelinated fibers (Fig. 5 B, arrowheads) were not labeled with the L1 antibody. Exclusive detection of L1 in unmyelinated fibers in the PNS was consistent with previous reports (Martini and Schachner 1986).


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)

L1 is expressed by adult unmyelinated sensory but not sympathetic axons. In teased nerve fibers from P60 wild-type mouse dorsal root (A), L1 antibodies selectively stained unmyelinated fibers. L1 immunoreactivity surrounds the nucleus of a nonmyelinating Schwann cell (A, arrowhead) and confirms L1 expression by Schwann cells (A, arrows). L1 immunoreactivity in transverse cryosections of P60 wild-type nerve shows typical appearance of nonmyelinated fibers (B, arrows). Myelinated fibers (B, arrowheads) were not labeled with the L1 antibody. Sections (20 μm thick) from dorsal root ganglia (DRG) were double-labeled for L1 (C, red) and nonphosphorylated neurofilament (C, green). The plasma membrane (C, double arrowhead) and axon (C, arrowhead) of the small diameter neurons and the unmyelinated fibers (C, arrow) were L1-positive. Large diameter myelinated axons (C, asterisk) were labeled by neurofilament but not L1 antibodies. In sections (20 μm thick) of P60 DRG, small diameter neurons (D, arrows) were double-labeled for L1 (D, red) and Calcitonin gene-related product (CGRP) (D, green). The axons of these neurons were also L1-positive (D, arrowheads). In sections (20 μm thick) of P60 mouse superior cervical ganglia (SCG), neurons (E, arrowheads) and the axons exiting neuronal cell bodies were positive for neurofilament (green) but not for L1 (red). The nonmyelinating Schwann cells surrounding the SCG axons were L1-positive (E, arrow). Bars: (A) 30 μm; (B–D) 10 μm; (E) 25 μm.
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Figure 5: L1 is expressed by adult unmyelinated sensory but not sympathetic axons. In teased nerve fibers from P60 wild-type mouse dorsal root (A), L1 antibodies selectively stained unmyelinated fibers. L1 immunoreactivity surrounds the nucleus of a nonmyelinating Schwann cell (A, arrowhead) and confirms L1 expression by Schwann cells (A, arrows). L1 immunoreactivity in transverse cryosections of P60 wild-type nerve shows typical appearance of nonmyelinated fibers (B, arrows). Myelinated fibers (B, arrowheads) were not labeled with the L1 antibody. Sections (20 μm thick) from dorsal root ganglia (DRG) were double-labeled for L1 (C, red) and nonphosphorylated neurofilament (C, green). The plasma membrane (C, double arrowhead) and axon (C, arrowhead) of the small diameter neurons and the unmyelinated fibers (C, arrow) were L1-positive. Large diameter myelinated axons (C, asterisk) were labeled by neurofilament but not L1 antibodies. In sections (20 μm thick) of P60 DRG, small diameter neurons (D, arrows) were double-labeled for L1 (D, red) and Calcitonin gene-related product (CGRP) (D, green). The axons of these neurons were also L1-positive (D, arrowheads). In sections (20 μm thick) of P60 mouse superior cervical ganglia (SCG), neurons (E, arrowheads) and the axons exiting neuronal cell bodies were positive for neurofilament (green) but not for L1 (red). The nonmyelinating Schwann cells surrounding the SCG axons were L1-positive (E, arrow). Bars: (A) 30 μm; (B–D) 10 μm; (E) 25 μm.
Mentions: To investigate if the different phenotype in sensory and sympathetic unmyelinated fibers was due to differential expression of L1, the immunocytochemical localization of L1 was compared in dorsal roots and cervical sympathetic trunks from P60 wild-type mice. Unmyelinated fibers in teased fiber preparations from dorsal roots were positive for L1 (Fig. 5 A, arrows). L1 immunoprecipitate was clearly delineated in the nonmyelinating Schwann cells. In transverse one micron thick cryosections from P60 wild-type mouse sciatic nerve L1 antibodies also stained the Schwann cells of unmyelinated fibers (Fig. 5 B, arrows). However, the optical resolution of immunostaining in these preparations was insufficient to determine whether L1 was also present in the small diameter axons. Myelinated fibers (Fig. 5 B, arrowheads) were not labeled with the L1 antibody. Exclusive detection of L1 in unmyelinated fibers in the PNS was consistent with previous reports (Martini and Schachner 1986).

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