Cadherin expression in the somatosensory cortex: evidence for a combinatorial molecular code at the single-cell level
ABSTRACT Cadherin superfamily genes play a role in a wide variety of developmental processes and mature functions of the vertebrate brain. In the present study, we mapped in situ the expression pattern of five classic cadherins (Cdh4, Cdh6, Cdh7, Cdh8, Cdh11) and eight δ-protocadherins (Pcdh1, Pcdh7, Pcdh8, Pcdh9, Pcdh10, Pcdh11, Pcdh17 and Pcdh19) in the primary somatosensory cortex of the adult mouse. All of these cadherins show layer-specific expression profiles in primary somatosensory cortex. Some cadherins (for example, Cdh4, Cdh7, Pcdh8) mark subsets of cells within a given lamina, while other cadherins (Cdh11 and Pcdh10) are expressed more widely in multiple layers. Results from tyramide-based double-fluorescence in situ hybridization (FISH) provide evidence that most single neurons express more than one cadherin in a combinatorial fashion in all layers of cerebral cortex. This combinatorial code is rather comprehensive because pairwise expression of cadherins can assume any type of combination (complementarity, partial or complete overlap, subset-specific expression, cell-size specific expression, etc.). We propose that the combinatorial expression of multiple cadherin genes contributes to the molecular specification of the vast complexity of neurons in cerebral cortex.
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ABSTRACT: The type II classic cadherin subfamily contains a number of extensively studied genes (cdh6, cdh8, cdh11); however, the expression and function of the other members have only been partially described. Here we employed reverse-transcription polymerase chain reaction (RT-PCR) and in situ hybridization to characterize cortical and hippocampal expression of all type II cadherins (with the exception of the nonneural Cdh5) in the developing and adult mouse brain. Many of these genes have ubiquitous mRNA distribution patterns throughout development, indicating high functional redundancy, which might be necessary for safe production of the strictly laminated structure of these regions. A few of the genes examined, however, exhibit a unique spatiotemporal pattern of expression, particularly during cortical development, indicating a potentially specific function. In the developing and adult hippocampus, almost all of these genes are strongly expressed in glutamatergic neurons of the CA1-CA3 pyramidal cell layer and the granular layer of the dentate gyrus. In contrast, there are significant expression differences within the GABAergic cells of the adult hippocampus. Our results indicate that selective expression of type II cadherins may generate a flexible cell-adhesion machinery for developing neurons to selectively bind to each other, but can also provide a high level of security due to the multiple overlaps in the expression domains.The Journal of Comparative Neurology 05/2012; 520(7):1387-1405. DOI:10.1002/cne.22801 · 3.51 Impact Factor
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ABSTRACT: Fusobacterium nucleatum is a Gram-negative oral anaerobe, capable of systemic dissemination causing infections and abscesses, often in mixed-species, at different body sites. We have shown previously that F. nucleatum adheres to and invades host epithelial and endothelial cells via a novel FadA adhesin. In this study, vascular endothelial (VE)-cadherin, a member of the cadherin family and a cell-cell junction molecule, was identified as the endothelial receptor for FadA, required for F. nucleatum binding to the cells. FadA colocalized with VE-cadherin on endothelial cells, causing relocation of VE-cadherin away from the cell-cell junctions. As a result, the endothelial permeability was increased, allowing the bacteria to cross the endothelium through loosened junctions. This crossing mechanism may explain why the organism is able to disseminate systemically to colonize in different body sites and even overcome the placental and blood-brain barriers. Co-incubation of F. nucleatum and Escherichia coli enhanced penetration of the endothelial cells by the latter in the transwell assays, suggesting F. nucleatum may serve as an 'enabler' for other microorganisms to spread systemically. This may explain why F. nucleatum is often found in mixed infections. This study reveals a possible novel dissemination mechanism utilized by pathogens.Molecular Microbiology 12/2011; 82(6):1468-80. DOI:10.1111/j.1365-2958.2011.07905.x · 5.03 Impact Factor
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ABSTRACT: The sarcoglycan complex, consisting of α-, β-, γ-, δ- and ε-sarcoglycans, is a multimember transmembrane system providing a mechanosignaling connection from the cytoskeleton to the extracellular matrix. Whereas the expression of α- and γ-sarcoglycan is restricted to striated muscle, other sarcoglycans are widely expressed. Although many studies have investigated sarcoglycans in all muscle types, insufficient data are available on the distribution of the sarcoglycan complex in nonmuscle tissue. On this basis, we used immunohistochemical and RT-PCR techniques to study preliminarily the sarcoglycans in normal glandular breast tissue (which has never been studied in the literature on these proteins) to verify the effective wider distribution of this complex. Moreover, to understand the role of sarcoglycans, we also tested samples obtained from patients affected by fibrocystic mastopathy and breast fibroadenoma. Our data showed, for the first time, that all sarcoglycans are always detectable in all normal samples both in epithelial and myoepithelial cells; in pathological breast tissue, all sarcoglycans appeared severely reduced. These data demonstrated that all sarcoglycans, not only β-, δ-, and ε-sarcoglycans, have a wider distribution, implying a new unknown role for these proteins. Moreover, in breast diseases, sarcoglycans containing cadherin domain homologs could provoke a loss of strong adhesion between epithelial cells, permitting and facilitating the degeneration of these benign breast tumors into malignant tumors. Consequently, sarcoglycans could play an important and intriguing role in many breast diseases and in particular in tumor progression from benign to malignant.Cells Tissues Organs 01/2011; 195(6):550-562. DOI:10.1159/000329508 · 2.14 Impact Factor