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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

The adult barrelfield in tangential sections. Nissl staining (A,B) of tangential sections show the PosteroMedial Barrel SubField (PMBSF) and the AnteroLateral Barrel SubField (ALBSF) subdivisions of the primary somatosensory area. The PMBSF barrels displayed blurred septa in  mutant mice, and ALBSF barrels were less distinct in mutant than in wild type mice. Cytochrome oxidase histochemistry (C,D) was used to assess possible changes in  mutant mice. The dotted lines delineate the part of the PMBSF containing the straddler barrels (α–δ) and the first posteromedial barrels of each row A to E (A1–A3, B1–B4, C1–C5, D1–D5, E1–E5); these barrels seemed unmodified in mutant animals. On the contrary, the rostrolateral barrels in the PMBSF and the barrels in the ALBSF were blurred and indistinct in mutant mice, suggesting that the genetic deletion of NCAM causes selective topographical changes in the somatosensory map. Images are reconstructions of serial sections. Bar: 1 mm.
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Figure 9: The adult barrelfield in tangential sections. Nissl staining (A,B) of tangential sections show the PosteroMedial Barrel SubField (PMBSF) and the AnteroLateral Barrel SubField (ALBSF) subdivisions of the primary somatosensory area. The PMBSF barrels displayed blurred septa in mutant mice, and ALBSF barrels were less distinct in mutant than in wild type mice. Cytochrome oxidase histochemistry (C,D) was used to assess possible changes in mutant mice. The dotted lines delineate the part of the PMBSF containing the straddler barrels (α–δ) and the first posteromedial barrels of each row A to E (A1–A3, B1–B4, C1–C5, D1–D5, E1–E5); these barrels seemed unmodified in mutant animals. On the contrary, the rostrolateral barrels in the PMBSF and the barrels in the ALBSF were blurred and indistinct in mutant mice, suggesting that the genetic deletion of NCAM causes selective topographical changes in the somatosensory map. Images are reconstructions of serial sections. Bar: 1 mm.

Mentions: Then, we analyzed the somatosensory map in tangential sections of the cortex for the occurrence of topographic changes in adult NCAM mutants. The posteromedial barrel subfield (PMBSF) contains a group of large, ovoid barrels whose topographic distribution is homeomorphic to that of the largest vibrissa follicles of the animal's snout. The anterolateral barrel subfield (ALBSF) contains similar yet smaller barrels, which correspond to the smallest and less prominent whiskers of the animal's face. As shown in tangential reconstructions of Nissl staining (Figures 9A,B), the barrel septa were less prominent in mutant mice (n = 4) than in wild type mice (n = 4) and were indiscernible at rostral positions within the PMBSF of mutant mice (Figure 9B). Cytochrome oxidase staining delineated distinct barrels in both genotypes (wild type, n = 4; mutant, n = 6). However, in mutant mice, only the most caudomedial part of the PMBSF that contains the straddler barrels (α–δ) and the first large barrels of rows A–E, showed such a clear delineation and their overall topography seemed unchanged (Figures 9C,D). The other barrels in the PMBSF and in the entire ALBSF were profoundly altered in mutant mice, and were virtually indistinct. Both Nissl staining and cytochrome oxidase histochemistry unveiled a prominent phenotype trait, the disruption of barrels in the ALBSF and of the most rostral barrels in the PMBSF. These alterations in the barrel field of the somatosensory cortex suggested that the regional alteration of NCAM TC axons might contribute to disrupted topographic mapping, and that NCAM may be required for the topographical anatomical distribution of TC axons in the somatosensory cortex.


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)

The adult barrelfield in tangential sections. Nissl staining (A,B) of tangential sections show the PosteroMedial Barrel SubField (PMBSF) and the AnteroLateral Barrel SubField (ALBSF) subdivisions of the primary somatosensory area. The PMBSF barrels displayed blurred septa in  mutant mice, and ALBSF barrels were less distinct in mutant than in wild type mice. Cytochrome oxidase histochemistry (C,D) was used to assess possible changes in  mutant mice. The dotted lines delineate the part of the PMBSF containing the straddler barrels (α–δ) and the first posteromedial barrels of each row A to E (A1–A3, B1–B4, C1–C5, D1–D5, E1–E5); these barrels seemed unmodified in mutant animals. On the contrary, the rostrolateral barrels in the PMBSF and the barrels in the ALBSF were blurred and indistinct in mutant mice, suggesting that the genetic deletion of NCAM causes selective topographical changes in the somatosensory map. Images are reconstructions of serial sections. Bar: 1 mm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3378950&req=5

Figure 9: The adult barrelfield in tangential sections. Nissl staining (A,B) of tangential sections show the PosteroMedial Barrel SubField (PMBSF) and the AnteroLateral Barrel SubField (ALBSF) subdivisions of the primary somatosensory area. The PMBSF barrels displayed blurred septa in mutant mice, and ALBSF barrels were less distinct in mutant than in wild type mice. Cytochrome oxidase histochemistry (C,D) was used to assess possible changes in mutant mice. The dotted lines delineate the part of the PMBSF containing the straddler barrels (α–δ) and the first posteromedial barrels of each row A to E (A1–A3, B1–B4, C1–C5, D1–D5, E1–E5); these barrels seemed unmodified in mutant animals. On the contrary, the rostrolateral barrels in the PMBSF and the barrels in the ALBSF were blurred and indistinct in mutant mice, suggesting that the genetic deletion of NCAM causes selective topographical changes in the somatosensory map. Images are reconstructions of serial sections. Bar: 1 mm.
Mentions: Then, we analyzed the somatosensory map in tangential sections of the cortex for the occurrence of topographic changes in adult NCAM mutants. The posteromedial barrel subfield (PMBSF) contains a group of large, ovoid barrels whose topographic distribution is homeomorphic to that of the largest vibrissa follicles of the animal's snout. The anterolateral barrel subfield (ALBSF) contains similar yet smaller barrels, which correspond to the smallest and less prominent whiskers of the animal's face. As shown in tangential reconstructions of Nissl staining (Figures 9A,B), the barrel septa were less prominent in mutant mice (n = 4) than in wild type mice (n = 4) and were indiscernible at rostral positions within the PMBSF of mutant mice (Figure 9B). Cytochrome oxidase staining delineated distinct barrels in both genotypes (wild type, n = 4; mutant, n = 6). However, in mutant mice, only the most caudomedial part of the PMBSF that contains the straddler barrels (α–δ) and the first large barrels of rows A–E, showed such a clear delineation and their overall topography seemed unchanged (Figures 9C,D). The other barrels in the PMBSF and in the entire ALBSF were profoundly altered in mutant mice, and were virtually indistinct. Both Nissl staining and cytochrome oxidase histochemistry unveiled a prominent phenotype trait, the disruption of barrels in the ALBSF and of the most rostral barrels in the PMBSF. These alterations in the barrel field of the somatosensory cortex suggested that the regional alteration of NCAM TC axons might contribute to disrupted topographic mapping, and that NCAM may be required for the topographical anatomical distribution of TC axons in the somatosensory cortex.

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