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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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Loss of L1 results in decreased sensory axons and reduced sensory function. (A) All unmyelinated axons in the fourth and fifth lumbar dorsal roots of five control, four L1-deficient, and four L1/MAG-deficient mice were counted in electron micrograph montages (×4200). Compared with control nerves, a 30–35% decrease in the number of unmyelinated axons was detected in L4 and L5 dorsal roots from L1-deficient and L1/MAG-deficient mice. *P < 0.01 according to the Student's t test. (B) The von Frey pressure test used the Semmes-Weinstein monofilaments to assay sensitivity to deep pressure. All control mice (n = 9) responded to the monofilament corresponding to 1.202 grams of force. In contrast, the L1-deficient mice (n = 7) responded to monofilament force ranging from 2.041–11.749 grams of pressure. *P < 0.015 according to the Student's t test.
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Figure 4: Loss of L1 results in decreased sensory axons and reduced sensory function. (A) All unmyelinated axons in the fourth and fifth lumbar dorsal roots of five control, four L1-deficient, and four L1/MAG-deficient mice were counted in electron micrograph montages (×4200). Compared with control nerves, a 30–35% decrease in the number of unmyelinated axons was detected in L4 and L5 dorsal roots from L1-deficient and L1/MAG-deficient mice. *P < 0.01 according to the Student's t test. (B) The von Frey pressure test used the Semmes-Weinstein monofilaments to assay sensitivity to deep pressure. All control mice (n = 9) responded to the monofilament corresponding to 1.202 grams of force. In contrast, the L1-deficient mice (n = 7) responded to monofilament force ranging from 2.041–11.749 grams of pressure. *P < 0.015 according to the Student's t test.

Mentions: Ultrastructural changes in L1-deficient unmyelinated axons were consistent with ongoing axonal degeneration. To extend this observation, the number of nonmyelinated axons was quantified in electron micrograph montages of the entire fourth and fifth lumbar dorsal roots from five wild-type, four L1-deficient, and four MAG/L1-deficient mice (Fig. 4 A). Lumbar dorsal roots 4 and 5 (L4 and L5) from L1-deficient and L1/MAG-deficient mice showed a 30 and 35% decrease of unmyelinated axons compared with wild-type L4 and L5 dorsal roots. This difference was statistically significant (P < 0.01) using the Student's t test. Myelinated fiber number was similar in control, L1-deficient, and L1/MAG-deficient dorsal roots (data not shown), indicating that the loss of unmyelinated axons is not a result of an increase in myelinated fibers. In addition, the number of nonmyelinating Schwann cell nuclei per unit area was not significantly different between control and L1-deficient mice (data not shown).


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)

Loss of L1 results in decreased sensory axons and reduced sensory function. (A) All unmyelinated axons in the fourth and fifth lumbar dorsal roots of five control, four L1-deficient, and four L1/MAG-deficient mice were counted in electron micrograph montages (×4200). Compared with control nerves, a 30–35% decrease in the number of unmyelinated axons was detected in L4 and L5 dorsal roots from L1-deficient and L1/MAG-deficient mice. *P < 0.01 according to the Student's t test. (B) The von Frey pressure test used the Semmes-Weinstein monofilaments to assay sensitivity to deep pressure. All control mice (n = 9) responded to the monofilament corresponding to 1.202 grams of force. In contrast, the L1-deficient mice (n = 7) responded to monofilament force ranging from 2.041–11.749 grams of pressure. *P < 0.015 according to the Student's t test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2169489&req=5

Figure 4: Loss of L1 results in decreased sensory axons and reduced sensory function. (A) All unmyelinated axons in the fourth and fifth lumbar dorsal roots of five control, four L1-deficient, and four L1/MAG-deficient mice were counted in electron micrograph montages (×4200). Compared with control nerves, a 30–35% decrease in the number of unmyelinated axons was detected in L4 and L5 dorsal roots from L1-deficient and L1/MAG-deficient mice. *P < 0.01 according to the Student's t test. (B) The von Frey pressure test used the Semmes-Weinstein monofilaments to assay sensitivity to deep pressure. All control mice (n = 9) responded to the monofilament corresponding to 1.202 grams of force. In contrast, the L1-deficient mice (n = 7) responded to monofilament force ranging from 2.041–11.749 grams of pressure. *P < 0.015 according to the Student's t test.
Mentions: Ultrastructural changes in L1-deficient unmyelinated axons were consistent with ongoing axonal degeneration. To extend this observation, the number of nonmyelinated axons was quantified in electron micrograph montages of the entire fourth and fifth lumbar dorsal roots from five wild-type, four L1-deficient, and four MAG/L1-deficient mice (Fig. 4 A). Lumbar dorsal roots 4 and 5 (L4 and L5) from L1-deficient and L1/MAG-deficient mice showed a 30 and 35% decrease of unmyelinated axons compared with wild-type L4 and L5 dorsal roots. This difference was statistically significant (P < 0.01) using the Student's t test. Myelinated fiber number was similar in control, L1-deficient, and L1/MAG-deficient dorsal roots (data not shown), indicating that the loss of unmyelinated axons is not a result of an increase in myelinated fibers. In addition, the number of nonmyelinating Schwann cell nuclei per unit area was not significantly different between control and L1-deficient mice (data not shown).

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