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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 barrelfield in the adult somatosensory cortex. In wild type animals (A), Nissl staining revealed individual cytoarchitectonic units (barrels) in layer IV of the somatosensory cortex. In contrast, Nissl staining of NCAM mutant mice (B) showed less distinct barrels. (C,D) Enlarged views of the areas marked with asterisks in (A,B). While septa were evident in wild type animals (C),  mutant mice (D) lacked well-delineated septa and layer IV cells formed horizontally placed microlaminae in knockout mice. (E,F) Cytochrome oxidase histochemistry of coronal sections revealed no obvious changes between wild type and  mutant mice. Bars: A, B, 1 mm (in A); C, D, 200 μm (in C); E, F, 200 μm (in E).
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Figure 8: The barrelfield in the adult somatosensory cortex. In wild type animals (A), Nissl staining revealed individual cytoarchitectonic units (barrels) in layer IV of the somatosensory cortex. In contrast, Nissl staining of NCAM mutant mice (B) showed less distinct barrels. (C,D) Enlarged views of the areas marked with asterisks in (A,B). While septa were evident in wild type animals (C), mutant mice (D) lacked well-delineated septa and layer IV cells formed horizontally placed microlaminae in knockout mice. (E,F) Cytochrome oxidase histochemistry of coronal sections revealed no obvious changes between wild type and mutant mice. Bars: A, B, 1 mm (in A); C, D, 200 μm (in C); E, F, 200 μm (in E).

Mentions: Nissl staining of coronal sections of adult brains revealed mild disruptions of the somatosensory map in NCAM mutant mice (Figures 8A–D). As compared to the well-defined barrels of wild type animals (n = 5) due to the presence of distinct barrel septa, mutant mice (n = 5) showed indistinct barrels with no discernible septa between them (Figures 8A,C) and the Nissl stain revealed a microlaminar deposition of cells within layer IV (Figures 8C,D). These changes occurred through all antero-posterior levels of the somatosensory area of the cortex. Layer IV of the somatosensory cortex in mutant mice remained prominent, suggesting reorganization of TC axons (Figures 8A–B). Cytochrome oxidase histochemistry (Wong-Riley and Welt, 1980) in coronal sections highlighted individual barrels in mutant mice (n = 3), though the staining was fainter in mice as compared to their wild type (n = 3) littermates, as shown for rostral barrels (Figures 8E,F). This was taken as an indication that the overall organization of the somatosensory cortex was preserved in mutant mice, although the refined cytoarchitectonic organization of the barrels was somewhat altered, indicating that layer IV neurons could be abnormally deployed in the barrels and septa.


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 barrelfield in the adult somatosensory cortex. In wild type animals (A), Nissl staining revealed individual cytoarchitectonic units (barrels) in layer IV of the somatosensory cortex. In contrast, Nissl staining of NCAM mutant mice (B) showed less distinct barrels. (C,D) Enlarged views of the areas marked with asterisks in (A,B). While septa were evident in wild type animals (C),  mutant mice (D) lacked well-delineated septa and layer IV cells formed horizontally placed microlaminae in knockout mice. (E,F) Cytochrome oxidase histochemistry of coronal sections revealed no obvious changes between wild type and  mutant mice. Bars: A, B, 1 mm (in A); C, D, 200 μm (in C); E, F, 200 μm (in E).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 8: The barrelfield in the adult somatosensory cortex. In wild type animals (A), Nissl staining revealed individual cytoarchitectonic units (barrels) in layer IV of the somatosensory cortex. In contrast, Nissl staining of NCAM mutant mice (B) showed less distinct barrels. (C,D) Enlarged views of the areas marked with asterisks in (A,B). While septa were evident in wild type animals (C), mutant mice (D) lacked well-delineated septa and layer IV cells formed horizontally placed microlaminae in knockout mice. (E,F) Cytochrome oxidase histochemistry of coronal sections revealed no obvious changes between wild type and mutant mice. Bars: A, B, 1 mm (in A); C, D, 200 μm (in C); E, F, 200 μm (in E).
Mentions: Nissl staining of coronal sections of adult brains revealed mild disruptions of the somatosensory map in NCAM mutant mice (Figures 8A–D). As compared to the well-defined barrels of wild type animals (n = 5) due to the presence of distinct barrel septa, mutant mice (n = 5) showed indistinct barrels with no discernible septa between them (Figures 8A,C) and the Nissl stain revealed a microlaminar deposition of cells within layer IV (Figures 8C,D). These changes occurred through all antero-posterior levels of the somatosensory area of the cortex. Layer IV of the somatosensory cortex in mutant mice remained prominent, suggesting reorganization of TC axons (Figures 8A–B). Cytochrome oxidase histochemistry (Wong-Riley and Welt, 1980) in coronal sections highlighted individual barrels in mutant mice (n = 3), though the staining was fainter in mice as compared to their wild type (n = 3) littermates, as shown for rostral barrels (Figures 8E,F). This was taken as an indication that the overall organization of the somatosensory cortex was preserved in mutant mice, although the refined cytoarchitectonic organization of the barrels was somewhat altered, indicating that layer IV neurons could be abnormally deployed in the barrels and septa.

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