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Neural cell adhesion molecule, NCAM, regulates thalamocortical axon pathfinding and the organization of the cortical somatosensory representation in mouse.

Enriquez-Barreto L, Palazzetti C, Brennaman LH, Maness PF, Fairén A - Front Mol Neurosci (2012)

Bottom Line: During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM mutant animals.NCAM mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex.These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández San Juan de Alicante, Spain.

ABSTRACT
To study the potential role of neural cell adhesion molecule (NCAM) in the development of thalamocortical (TC) axon topography, wild type, and NCAM mutant mice were analyzed for NCAM expression, projection, and targeting of TC afferents within the somatosensory area of the neocortex. Here we report that NCAM and its α-2,8-linked polysialic acid (PSA) are expressed in developing TC axons during projection to the neocortex. Pathfinding of TC axons in wild type and mutant mice was mapped using anterograde DiI labeling. At embryonic day E16.5, mutant mice displayed misguided TC axons in the dorsal telencephalon, but not in the ventral telencephalon, an intermediate target that initially sorts TC axons toward correct neocortical areas. During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM mutant animals. NCAM mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex. As shown by Nissl and cytochrome oxidase staining, barrels of the anterolateral barrel subfield (ALBSF) and the most distal barrels of the posteromedial barrel subfield (PMBSF) did not segregate properly in mutant mice. These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex.

No MeSH data available.


Related in: MedlinePlus

Expression of NCAM and oligopolysialylated NCAM in thalamocortical axons in the dorsal thalamus at E13.5. (A–A”) TC axons co-labeled by L1 and NCAM antibodies in wild type mice. (B–B”) In NCAM  mutant mice, NCAM immunostaining was absent, confirming the specificity of monoclonal antibody P61 in our material. (C–C”,D–D”) PSA immunoreactivity was present in L1-immunoreactive axons in the dorsal thalamus of wild type mice (C) but absent in NCAM  mice (D), suggesting that PSA is linked to NCAM in these axons. L1-immunoreactive TC axons formed descending fascicles that converged into the caudal limb of the internal capsule (ic) leading through the ventral telencephalon to the developing cortex. Single confocal optical sections. DT, dorsal thalamus; ic, internal capsule. Bar (in A): 100 μm.
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Figure 2: Expression of NCAM and oligopolysialylated NCAM in thalamocortical axons in the dorsal thalamus at E13.5. (A–A”) TC axons co-labeled by L1 and NCAM antibodies in wild type mice. (B–B”) In NCAM mutant mice, NCAM immunostaining was absent, confirming the specificity of monoclonal antibody P61 in our material. (C–C”,D–D”) PSA immunoreactivity was present in L1-immunoreactive axons in the dorsal thalamus of wild type mice (C) but absent in NCAM mice (D), suggesting that PSA is linked to NCAM in these axons. L1-immunoreactive TC axons formed descending fascicles that converged into the caudal limb of the internal capsule (ic) leading through the ventral telencephalon to the developing cortex. Single confocal optical sections. DT, dorsal thalamus; ic, internal capsule. Bar (in A): 100 μm.

Mentions: Next, wild type and NCAM mutant E13.5 and E15.5 mice (Cremer et al., 1994) were immunolabeled with antibodies to NCAM or PSA along with L1, which labels TC axons (Chung et al., 1991; Fukuda et al., 1997; Demyanenko et al., 2011b). L1-immunoreactive axons expressed transmembrane NCAM isoforms, as detected with a monoclonal antibody (mAb P61) that recognizes the cytoplasmic domain of both NCAM140 and NCAM180 (Figures 2A–A” and 3A–A”; Gennarini et al., 1984), but not NCAM120. NCAM immunoreactivity was absent in NCAM mutant mice (Figures 2B–B” and 3B–B”), demonstrating the specificity of this antibody. Using monoclonal antibody 12E3 that reacts with small chains of PSA (Seki and Arai, 1991; Nadanaka et al., 2001), we found that L1-expressing TC axons displayed immunoreactivity for PSA of low sialic acid content in wild type mice (Figures 2C–C” and 3C–C”). In NCAM mutant mice, 12E3 immunoreactivity was abolished (Figures 2D–D” and 3D–D”), suggesting that NCAM was the only carrier of PSA in TC axons at this stage (Seki and Arai, 1993; Cremer et al., 1997; Dityatev et al., 2004). NCAM and PSA exhibited similar patterns of immunoreactivity. PSA showed more extensive labeling than NCAM, which may be due to antibody sensitivity or PSA linkage to NCAM120, secreted NCAM, or other splice variants not recognized by our NCAM antibody. However, very little NCAM120 is present at this stage (Edelman and Chuong, 1982; Brennaman and Maness, 2008).


Neural cell adhesion molecule, NCAM, regulates thalamocortical axon pathfinding and the organization of the cortical somatosensory representation in mouse.

Enriquez-Barreto L, Palazzetti C, Brennaman LH, Maness PF, Fairén A - Front Mol Neurosci (2012)

Expression of NCAM and oligopolysialylated NCAM in thalamocortical axons in the dorsal thalamus at E13.5. (A–A”) TC axons co-labeled by L1 and NCAM antibodies in wild type mice. (B–B”) In NCAM  mutant mice, NCAM immunostaining was absent, confirming the specificity of monoclonal antibody P61 in our material. (C–C”,D–D”) PSA immunoreactivity was present in L1-immunoreactive axons in the dorsal thalamus of wild type mice (C) but absent in NCAM  mice (D), suggesting that PSA is linked to NCAM in these axons. L1-immunoreactive TC axons formed descending fascicles that converged into the caudal limb of the internal capsule (ic) leading through the ventral telencephalon to the developing cortex. Single confocal optical sections. DT, dorsal thalamus; ic, internal capsule. Bar (in A): 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 2: Expression of NCAM and oligopolysialylated NCAM in thalamocortical axons in the dorsal thalamus at E13.5. (A–A”) TC axons co-labeled by L1 and NCAM antibodies in wild type mice. (B–B”) In NCAM mutant mice, NCAM immunostaining was absent, confirming the specificity of monoclonal antibody P61 in our material. (C–C”,D–D”) PSA immunoreactivity was present in L1-immunoreactive axons in the dorsal thalamus of wild type mice (C) but absent in NCAM mice (D), suggesting that PSA is linked to NCAM in these axons. L1-immunoreactive TC axons formed descending fascicles that converged into the caudal limb of the internal capsule (ic) leading through the ventral telencephalon to the developing cortex. Single confocal optical sections. DT, dorsal thalamus; ic, internal capsule. Bar (in A): 100 μm.
Mentions: Next, wild type and NCAM mutant E13.5 and E15.5 mice (Cremer et al., 1994) were immunolabeled with antibodies to NCAM or PSA along with L1, which labels TC axons (Chung et al., 1991; Fukuda et al., 1997; Demyanenko et al., 2011b). L1-immunoreactive axons expressed transmembrane NCAM isoforms, as detected with a monoclonal antibody (mAb P61) that recognizes the cytoplasmic domain of both NCAM140 and NCAM180 (Figures 2A–A” and 3A–A”; Gennarini et al., 1984), but not NCAM120. NCAM immunoreactivity was absent in NCAM mutant mice (Figures 2B–B” and 3B–B”), demonstrating the specificity of this antibody. Using monoclonal antibody 12E3 that reacts with small chains of PSA (Seki and Arai, 1991; Nadanaka et al., 2001), we found that L1-expressing TC axons displayed immunoreactivity for PSA of low sialic acid content in wild type mice (Figures 2C–C” and 3C–C”). In NCAM mutant mice, 12E3 immunoreactivity was abolished (Figures 2D–D” and 3D–D”), suggesting that NCAM was the only carrier of PSA in TC axons at this stage (Seki and Arai, 1993; Cremer et al., 1997; Dityatev et al., 2004). NCAM and PSA exhibited similar patterns of immunoreactivity. PSA showed more extensive labeling than NCAM, which may be due to antibody sensitivity or PSA linkage to NCAM120, secreted NCAM, or other splice variants not recognized by our NCAM antibody. However, very little NCAM120 is present at this stage (Edelman and Chuong, 1982; Brennaman and Maness, 2008).

Bottom Line: During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM mutant animals.NCAM mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex.These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández San Juan de Alicante, Spain.

ABSTRACT
To study the potential role of neural cell adhesion molecule (NCAM) in the development of thalamocortical (TC) axon topography, wild type, and NCAM mutant mice were analyzed for NCAM expression, projection, and targeting of TC afferents within the somatosensory area of the neocortex. Here we report that NCAM and its α-2,8-linked polysialic acid (PSA) are expressed in developing TC axons during projection to the neocortex. Pathfinding of TC axons in wild type and mutant mice was mapped using anterograde DiI labeling. At embryonic day E16.5, mutant mice displayed misguided TC axons in the dorsal telencephalon, but not in the ventral telencephalon, an intermediate target that initially sorts TC axons toward correct neocortical areas. During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM mutant animals. NCAM mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex. As shown by Nissl and cytochrome oxidase staining, barrels of the anterolateral barrel subfield (ALBSF) and the most distal barrels of the posteromedial barrel subfield (PMBSF) did not segregate properly in mutant mice. These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex.

No MeSH data available.


Related in: MedlinePlus