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The importance of combinatorial gene expression in early Mammalian thalamic patterning and thalamocortical axonal guidance.

Price DJ, Clegg J, Duocastella XO, Willshaw D, Pratt T - Front Neurosci (2012)

Bottom Line: Mechanisms include guidance by previously generated guidepost cells, such as those in the subpallium that maintain thalamic axonal order and direction, and axons such as those of reciprocal projections from intermediate structures or from the cortex itself back toward the thalamus.We show how thalamocortical pathfinding involves numerous guidance cues operating at a series of steps along their route.We stress the importance of the combinatorial actions of multiple genes for the development of the numerous specific identities and functions of cells in this exquisitely complex system and their orderly innervation of the cortex.

View Article: PubMed Central - PubMed

Affiliation: Centre for Integrative Physiology, University of Edinburgh Edinburgh, UK.

ABSTRACT
The thalamus is essential for sensory perception. In mammals, work on the mouse has taught us most of what we know about how it develops and connects to the cortex. The mature thalamus of all mammalian species comprises numerous anatomically distinct collections of neurons called nuclei that differ in function, connectivity, and molecular constitution. At the time of its initial appearance as a distinct structure following neural tube closure, the thalamus is already patterned by the regional expression of numerous regulatory genes. This patterning, which lays down the blueprint for later development of thalamic nuclei, predates the development of thalamocortical projections. In this review we apply novel analytical methods to gene expression data available in the Allen Developing Mouse Brain Atlas to highlight the complex organized molecular heterogeneity already present among cells in the thalamus from the earliest stages at which it contains differentiating neurons. This early patterning is likely to invest in axons growing from different parts of the thalamus the ability to navigate in an ordered way to their appropriate area in the cerebral cortex. We review the mechanisms and cues that thalamic axons use, encounter, and interpret to attain the cortex. Mechanisms include guidance by previously generated guidepost cells, such as those in the subpallium that maintain thalamic axonal order and direction, and axons such as those of reciprocal projections from intermediate structures or from the cortex itself back toward the thalamus. We show how thalamocortical pathfinding involves numerous guidance cues operating at a series of steps along their route. We stress the importance of the combinatorial actions of multiple genes for the development of the numerous specific identities and functions of cells in this exquisitely complex system and their orderly innervation of the cortex.

No MeSH data available.


Gbx2 and Otx2 co-expression in E13.5 thalamus. Top four panels show the raw data from ADMBA: in situ hybridizations for gbx2 and otx2 at two coronal levels through the thalamus (see Figure 6). The lower four panels show representations of gbx2 and otx2 co-expression obtained by combining gene expression and cell density information and calculating the (1) maximum and (2) minimum number of cells in each 20 μm × 20 μm tile co-expressing olig2 and otx2 (as in Figure 6). A strip of co-expressing cells, narrow in the mediolateral axis but extending along the dorsoventral axis of the thalamus, is identified where two to six cells in each tile must be co-expressing gbx2 and otx2.
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Figure 8: Gbx2 and Otx2 co-expression in E13.5 thalamus. Top four panels show the raw data from ADMBA: in situ hybridizations for gbx2 and otx2 at two coronal levels through the thalamus (see Figure 6). The lower four panels show representations of gbx2 and otx2 co-expression obtained by combining gene expression and cell density information and calculating the (1) maximum and (2) minimum number of cells in each 20 μm × 20 μm tile co-expressing olig2 and otx2 (as in Figure 6). A strip of co-expressing cells, narrow in the mediolateral axis but extending along the dorsoventral axis of the thalamus, is identified where two to six cells in each tile must be co-expressing gbx2 and otx2.

Mentions: The combination of minimum and maximum double-labeling values for each pair of genes provides information on the number of cells that must be co-expressing both genes and the potential number of cells that could. Examples of the outcomes of these analyses are shown in Figures 6–8. It is important to point out that these theoretical outcomes, which would need to be verified experimentally, necessarily involve assumptions. One of the assumptions, which might affect the estimates of minimum double-labeling, is that the expression pattern of each gene is similar through the depth of each 20 μm-thick section. This assumption might become less accurate in areas of high cell density in which, given an average cell diameter of about 10 μm, a maximum of two entire cells or one entire cell and two cell fragments might be located above each other at any point across the surface of the section. The more positions there are at which labeling is contributed by only one of the cells stacked above each other, the greater will be the overestimate of minimum double-labeling.


The importance of combinatorial gene expression in early Mammalian thalamic patterning and thalamocortical axonal guidance.

Price DJ, Clegg J, Duocastella XO, Willshaw D, Pratt T - Front Neurosci (2012)

Gbx2 and Otx2 co-expression in E13.5 thalamus. Top four panels show the raw data from ADMBA: in situ hybridizations for gbx2 and otx2 at two coronal levels through the thalamus (see Figure 6). The lower four panels show representations of gbx2 and otx2 co-expression obtained by combining gene expression and cell density information and calculating the (1) maximum and (2) minimum number of cells in each 20 μm × 20 μm tile co-expressing olig2 and otx2 (as in Figure 6). A strip of co-expressing cells, narrow in the mediolateral axis but extending along the dorsoventral axis of the thalamus, is identified where two to six cells in each tile must be co-expressing gbx2 and otx2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3304307&req=5

Figure 8: Gbx2 and Otx2 co-expression in E13.5 thalamus. Top four panels show the raw data from ADMBA: in situ hybridizations for gbx2 and otx2 at two coronal levels through the thalamus (see Figure 6). The lower four panels show representations of gbx2 and otx2 co-expression obtained by combining gene expression and cell density information and calculating the (1) maximum and (2) minimum number of cells in each 20 μm × 20 μm tile co-expressing olig2 and otx2 (as in Figure 6). A strip of co-expressing cells, narrow in the mediolateral axis but extending along the dorsoventral axis of the thalamus, is identified where two to six cells in each tile must be co-expressing gbx2 and otx2.
Mentions: The combination of minimum and maximum double-labeling values for each pair of genes provides information on the number of cells that must be co-expressing both genes and the potential number of cells that could. Examples of the outcomes of these analyses are shown in Figures 6–8. It is important to point out that these theoretical outcomes, which would need to be verified experimentally, necessarily involve assumptions. One of the assumptions, which might affect the estimates of minimum double-labeling, is that the expression pattern of each gene is similar through the depth of each 20 μm-thick section. This assumption might become less accurate in areas of high cell density in which, given an average cell diameter of about 10 μm, a maximum of two entire cells or one entire cell and two cell fragments might be located above each other at any point across the surface of the section. The more positions there are at which labeling is contributed by only one of the cells stacked above each other, the greater will be the overestimate of minimum double-labeling.

Bottom Line: Mechanisms include guidance by previously generated guidepost cells, such as those in the subpallium that maintain thalamic axonal order and direction, and axons such as those of reciprocal projections from intermediate structures or from the cortex itself back toward the thalamus.We show how thalamocortical pathfinding involves numerous guidance cues operating at a series of steps along their route.We stress the importance of the combinatorial actions of multiple genes for the development of the numerous specific identities and functions of cells in this exquisitely complex system and their orderly innervation of the cortex.

View Article: PubMed Central - PubMed

Affiliation: Centre for Integrative Physiology, University of Edinburgh Edinburgh, UK.

ABSTRACT
The thalamus is essential for sensory perception. In mammals, work on the mouse has taught us most of what we know about how it develops and connects to the cortex. The mature thalamus of all mammalian species comprises numerous anatomically distinct collections of neurons called nuclei that differ in function, connectivity, and molecular constitution. At the time of its initial appearance as a distinct structure following neural tube closure, the thalamus is already patterned by the regional expression of numerous regulatory genes. This patterning, which lays down the blueprint for later development of thalamic nuclei, predates the development of thalamocortical projections. In this review we apply novel analytical methods to gene expression data available in the Allen Developing Mouse Brain Atlas to highlight the complex organized molecular heterogeneity already present among cells in the thalamus from the earliest stages at which it contains differentiating neurons. This early patterning is likely to invest in axons growing from different parts of the thalamus the ability to navigate in an ordered way to their appropriate area in the cerebral cortex. We review the mechanisms and cues that thalamic axons use, encounter, and interpret to attain the cortex. Mechanisms include guidance by previously generated guidepost cells, such as those in the subpallium that maintain thalamic axonal order and direction, and axons such as those of reciprocal projections from intermediate structures or from the cortex itself back toward the thalamus. We show how thalamocortical pathfinding involves numerous guidance cues operating at a series of steps along their route. We stress the importance of the combinatorial actions of multiple genes for the development of the numerous specific identities and functions of cells in this exquisitely complex system and their orderly innervation of the cortex.

No MeSH data available.