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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

Thalamocortical axons labeled by DiI inserted into the dorsal thalamus at E16.5. (A,B) DiI-labeled TC axons followed the internal capsule in the ventral forebrain to reach the subplate. The inset shows the orientation of the vertical slices at 45° from the midsagittal plane used to image DiI labeling. In these sections, TC axons in the lateral part of the internal capsule are more anterior than those located medially. (C,D) TC axons started their entry into the cortical plate, but these axonal arborizations were visibly more profuse in wild type (C) than in NCAM  mice (D). Images are maximum projections of confocal optical sections, covering total thicknesses of 29 μm (A,B) or 11 μm (C,D). CP, cortical plate; ic, internal capsule; LGE, lateral ganglionic eminence; SP, subplate. Bars: 200 μm (A,B); 50 μm (C,D).
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Figure 4: Thalamocortical axons labeled by DiI inserted into the dorsal thalamus at E16.5. (A,B) DiI-labeled TC axons followed the internal capsule in the ventral forebrain to reach the subplate. The inset shows the orientation of the vertical slices at 45° from the midsagittal plane used to image DiI labeling. In these sections, TC axons in the lateral part of the internal capsule are more anterior than those located medially. (C,D) TC axons started their entry into the cortical plate, but these axonal arborizations were visibly more profuse in wild type (C) than in NCAM mice (D). Images are maximum projections of confocal optical sections, covering total thicknesses of 29 μm (A,B) or 11 μm (C,D). CP, cortical plate; ic, internal capsule; LGE, lateral ganglionic eminence; SP, subplate. Bars: 200 μm (A,B); 50 μm (C,D).

Mentions: Mice remained in 0.05 % azide in PBS for 3–4 weeks. Brains were then sectioned at 100 μm in a vertical plane oriented 45° with respect to the coronal plane, in order to recover the maximum number of TC axons in each single section (Agmon and Connors, 1991; see schematics in Figure 4). For combined DiI—immunofluorescence staining, selected sections from DiI injected brains were processed without detergents. Sections were mounted onto glass slides with Citifluor.


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)

Thalamocortical axons labeled by DiI inserted into the dorsal thalamus at E16.5. (A,B) DiI-labeled TC axons followed the internal capsule in the ventral forebrain to reach the subplate. The inset shows the orientation of the vertical slices at 45° from the midsagittal plane used to image DiI labeling. In these sections, TC axons in the lateral part of the internal capsule are more anterior than those located medially. (C,D) TC axons started their entry into the cortical plate, but these axonal arborizations were visibly more profuse in wild type (C) than in NCAM  mice (D). Images are maximum projections of confocal optical sections, covering total thicknesses of 29 μm (A,B) or 11 μm (C,D). CP, cortical plate; ic, internal capsule; LGE, lateral ganglionic eminence; SP, subplate. Bars: 200 μm (A,B); 50 μm (C,D).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Thalamocortical axons labeled by DiI inserted into the dorsal thalamus at E16.5. (A,B) DiI-labeled TC axons followed the internal capsule in the ventral forebrain to reach the subplate. The inset shows the orientation of the vertical slices at 45° from the midsagittal plane used to image DiI labeling. In these sections, TC axons in the lateral part of the internal capsule are more anterior than those located medially. (C,D) TC axons started their entry into the cortical plate, but these axonal arborizations were visibly more profuse in wild type (C) than in NCAM mice (D). Images are maximum projections of confocal optical sections, covering total thicknesses of 29 μm (A,B) or 11 μm (C,D). CP, cortical plate; ic, internal capsule; LGE, lateral ganglionic eminence; SP, subplate. Bars: 200 μm (A,B); 50 μm (C,D).
Mentions: Mice remained in 0.05 % azide in PBS for 3–4 weeks. Brains were then sectioned at 100 μm in a vertical plane oriented 45° with respect to the coronal plane, in order to recover the maximum number of TC axons in each single section (Agmon and Connors, 1991; see schematics in Figure 4). For combined DiI—immunofluorescence staining, selected sections from DiI injected brains were processed without detergents. Sections were mounted onto glass slides with Citifluor.

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