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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

Distribution of TC axons in the lower layers of the developing cerebral cortex in postnatal animals. (A,B) Distribution of TC preterminal axons in the cortical plate of P2 wild type (A) and mutant (B) mice. (C,D) Bar graphs showing the absence of modifications in the geometry of TC axons within the cortex in  mutant mice at P2 (C) and P4 (D). Bar: 50 μm.
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Figure 6: Distribution of TC axons in the lower layers of the developing cerebral cortex in postnatal animals. (A,B) Distribution of TC preterminal axons in the cortical plate of P2 wild type (A) and mutant (B) mice. (C,D) Bar graphs showing the absence of modifications in the geometry of TC axons within the cortex in mutant mice at P2 (C) and P4 (D). Bar: 50 μm.

Mentions: NCAM mutant mice consistently showed reduced packing density of DiI labeled TC axons in the developing cortex (Figures 6A,B) in spite of the variability of DiI labeling. However, it was unclear whether this was accompanied by changes in the TC axon arborizations within the postnatal cerebral cortex. Prompted by the finding by Yamamoto et al. (2000) that PSA removal alters the orientation and layer targeting of TC axons in slice culture experiments, we analyzed whether NCAM deletion likewise causes alterations in the branching patterns of preterminal TC axons labeled anterogradely with DiI. We studied two different ages corresponding to the first week after birth when segregation into barrels occurs, at P2 (WT, n = 6 hemispheres; KO, n = 6 hemispheres) and at P4 (WT, n = 7 hemispheres; KO, n = 10 hemispheres).


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)

Distribution of TC axons in the lower layers of the developing cerebral cortex in postnatal animals. (A,B) Distribution of TC preterminal axons in the cortical plate of P2 wild type (A) and mutant (B) mice. (C,D) Bar graphs showing the absence of modifications in the geometry of TC axons within the cortex in  mutant mice at P2 (C) and P4 (D). Bar: 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Distribution of TC axons in the lower layers of the developing cerebral cortex in postnatal animals. (A,B) Distribution of TC preterminal axons in the cortical plate of P2 wild type (A) and mutant (B) mice. (C,D) Bar graphs showing the absence of modifications in the geometry of TC axons within the cortex in mutant mice at P2 (C) and P4 (D). Bar: 50 μm.
Mentions: NCAM mutant mice consistently showed reduced packing density of DiI labeled TC axons in the developing cortex (Figures 6A,B) in spite of the variability of DiI labeling. However, it was unclear whether this was accompanied by changes in the TC axon arborizations within the postnatal cerebral cortex. Prompted by the finding by Yamamoto et al. (2000) that PSA removal alters the orientation and layer targeting of TC axons in slice culture experiments, we analyzed whether NCAM deletion likewise causes alterations in the branching patterns of preterminal TC axons labeled anterogradely with DiI. We studied two different ages corresponding to the first week after birth when segregation into barrels occurs, at P2 (WT, n = 6 hemispheres; KO, n = 6 hemispheres) and at P4 (WT, n = 7 hemispheres; KO, n = 10 hemispheres).

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