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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

DiI tracing of thalamocortical fibers at early postnatal ages. (A,B) At P0, thick fascicles of DiI-labeled TC axons traversed the ventral telencephalon in their way to the developing cortex. The course of TC axons along the internal capsule was straight in wild type embryos (A), where few axon collaterals dispersed laterally. In  mutant mice (B), TC axon fascicles in the lateral parts of the pathway bent abruptly, failing to reach the cortex; arrows point at selected examples of dispersed axon fascicles. Axons at more medial locations, although less dispersed, navigated in a disorderly manner, giving rise to abundant axon collaterals in the ventral telencephalon. Asterisks in A and B mark the inferior level of the internal capsule in the ventral telencephalon. (C,D) TC axons entering the lower tier of the cortical plate in wild type and knockout mice at P0. Null mutant mice showed less densely packed axonal arborizations than wild type mice. (E,F) At P2, compared to wild type mice (C), TC axons in the ventral telencephalon of  mutant mice (D) dispersed laterally; one extreme example is marked with an arrow. Null mutant mice showed sparser TC axons in the cortex than wild type mice. Arrowheads in E point to retrogradely DiI labeled neurons in the cortical plate. The subplate was identified as the level TC axons bend medially to adopt trajectories parallel to the palial surface. Maximum confocal projections. Bar: 100 μm.
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Figure 5: DiI tracing of thalamocortical fibers at early postnatal ages. (A,B) At P0, thick fascicles of DiI-labeled TC axons traversed the ventral telencephalon in their way to the developing cortex. The course of TC axons along the internal capsule was straight in wild type embryos (A), where few axon collaterals dispersed laterally. In mutant mice (B), TC axon fascicles in the lateral parts of the pathway bent abruptly, failing to reach the cortex; arrows point at selected examples of dispersed axon fascicles. Axons at more medial locations, although less dispersed, navigated in a disorderly manner, giving rise to abundant axon collaterals in the ventral telencephalon. Asterisks in A and B mark the inferior level of the internal capsule in the ventral telencephalon. (C,D) TC axons entering the lower tier of the cortical plate in wild type and knockout mice at P0. Null mutant mice showed less densely packed axonal arborizations than wild type mice. (E,F) At P2, compared to wild type mice (C), TC axons in the ventral telencephalon of mutant mice (D) dispersed laterally; one extreme example is marked with an arrow. Null mutant mice showed sparser TC axons in the cortex than wild type mice. Arrowheads in E point to retrogradely DiI labeled neurons in the cortical plate. The subplate was identified as the level TC axons bend medially to adopt trajectories parallel to the palial surface. Maximum confocal projections. Bar: 100 μm.

Mentions: NCAM removal caused a more visible phenotype of altered guidance of TC axons during early postnatal development. As TC axons course through the ventral telencephalon, their characteristic fan-like distribution as seen in the obliquely oriented vertical sections (Figure 5A) was altered in early postnatal NCAM mice with respect to wild type animals. In mutant P0 mice, TC axons navigated in a disorderly manner and, unlike in wild type mice, gave rise to local axon collaterals in the ventral telencephalon (Figures 5A,B). In addition, NCAM TC axons in the rostrolateral tier of the internal capsule became disoriented within the ventral telencephalon, bent abruptly at right angles (Figure 5B, arrows), and failed to reach the cortex unlike wild type mice (Figure 5A). The packing density of TC axons in the cortex in mutant mice (P0) was also visibly decreased, consistent with the observed disorientation (Figures 5C,D).


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)

DiI tracing of thalamocortical fibers at early postnatal ages. (A,B) At P0, thick fascicles of DiI-labeled TC axons traversed the ventral telencephalon in their way to the developing cortex. The course of TC axons along the internal capsule was straight in wild type embryos (A), where few axon collaterals dispersed laterally. In  mutant mice (B), TC axon fascicles in the lateral parts of the pathway bent abruptly, failing to reach the cortex; arrows point at selected examples of dispersed axon fascicles. Axons at more medial locations, although less dispersed, navigated in a disorderly manner, giving rise to abundant axon collaterals in the ventral telencephalon. Asterisks in A and B mark the inferior level of the internal capsule in the ventral telencephalon. (C,D) TC axons entering the lower tier of the cortical plate in wild type and knockout mice at P0. Null mutant mice showed less densely packed axonal arborizations than wild type mice. (E,F) At P2, compared to wild type mice (C), TC axons in the ventral telencephalon of  mutant mice (D) dispersed laterally; one extreme example is marked with an arrow. Null mutant mice showed sparser TC axons in the cortex than wild type mice. Arrowheads in E point to retrogradely DiI labeled neurons in the cortical plate. The subplate was identified as the level TC axons bend medially to adopt trajectories parallel to the palial surface. Maximum confocal projections. Bar: 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 5: DiI tracing of thalamocortical fibers at early postnatal ages. (A,B) At P0, thick fascicles of DiI-labeled TC axons traversed the ventral telencephalon in their way to the developing cortex. The course of TC axons along the internal capsule was straight in wild type embryos (A), where few axon collaterals dispersed laterally. In mutant mice (B), TC axon fascicles in the lateral parts of the pathway bent abruptly, failing to reach the cortex; arrows point at selected examples of dispersed axon fascicles. Axons at more medial locations, although less dispersed, navigated in a disorderly manner, giving rise to abundant axon collaterals in the ventral telencephalon. Asterisks in A and B mark the inferior level of the internal capsule in the ventral telencephalon. (C,D) TC axons entering the lower tier of the cortical plate in wild type and knockout mice at P0. Null mutant mice showed less densely packed axonal arborizations than wild type mice. (E,F) At P2, compared to wild type mice (C), TC axons in the ventral telencephalon of mutant mice (D) dispersed laterally; one extreme example is marked with an arrow. Null mutant mice showed sparser TC axons in the cortex than wild type mice. Arrowheads in E point to retrogradely DiI labeled neurons in the cortical plate. The subplate was identified as the level TC axons bend medially to adopt trajectories parallel to the palial surface. Maximum confocal projections. Bar: 100 μm.
Mentions: NCAM removal caused a more visible phenotype of altered guidance of TC axons during early postnatal development. As TC axons course through the ventral telencephalon, their characteristic fan-like distribution as seen in the obliquely oriented vertical sections (Figure 5A) was altered in early postnatal NCAM mice with respect to wild type animals. In mutant P0 mice, TC axons navigated in a disorderly manner and, unlike in wild type mice, gave rise to local axon collaterals in the ventral telencephalon (Figures 5A,B). In addition, NCAM TC axons in the rostrolateral tier of the internal capsule became disoriented within the ventral telencephalon, bent abruptly at right angles (Figure 5B, arrows), and failed to reach the cortex unlike wild type mice (Figure 5A). The packing density of TC axons in the cortex in mutant mice (P0) was also visibly decreased, consistent with the observed disorientation (Figures 5C,D).

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