Expression of a Novel Protocadherin, OL-Protocadherin, in a Subset of Functional Systems of the Developing Mouse Brain

Abstract

We cloned a novel protocadherin cDNA, which we named OL-protocadherin (OL-pc), from mouse brain cDNA libraries. Its cytoplasmic region showed no similarities to other protocadherins, indicating that it belongs to a novel subfamily of protocadherins. Experiments using transfectants showed that OL-pc is a homophilic cell-cell adhesion molecule. The molecular mass of OL-pc was 140 kDa in the brain. Expression of OL-pc mRNA was specific to the nervous system, changing over time from the embryonic stage to the adult stage. The OL-pc expression seemed to be restricted to a subset of functionally related brain nuclei and regions such as the nuclei in the main olfactory system, the limbic system, and the olivocortical projection. There were at least two distinct patterns of distribution for the OL-pc protein. First, it was localized in particular brain nuclei or compartments, such as the stripes of the developing cerebellum. Second, it was found at the synapse in regions such as the glomeruli of the olfactory bulb. In addition, the OL-pc protein seemed not to be detected or was detected only weakly in some regions, such as hippocampus in which the mRNA was expressed at high levels. These results indicate that the expression of OL-pc is developmentally regulated in a subset of the functional systems and that it may be involved in the formation of the neural network by segregation of the brain nuclei and mediation of the axonal connections.

Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation

“…The molecular mechanism of how PCDH10 inhibits tumor cell growth is unclear. The mouse Pcdh10 only weakly mediates cell aggregation (Hirano et al, 1999), indicating that cell-cell adhesion may not be its major function. PCDH10 is a typical protocadherin with a cytoplasmic motif, CM-2, homologous to a laminin-type EGF-like (LE) domain (Wolverton and Lalande, 2001).…”

Zebrafish protocadherin 10 is involved in paraxial mesoderm development and somitogenesis

“…We cloned a zebrafish ortholog of Pcdh10, which showed a high degree of similarity (73-74% identity) to the known counterparts in mouse (Hirano et al, 1999), human (Wolverton and Lalande, 2001), and chicken (accession no. NP 999837).…”

“…In 1-day and older embryos, it was also expressed in the diencephalon, the hindbrain, the otocyst epithelium, the eye muscles, and the fin buds. pcdh10 expression in the central nervous system (CNS) was described previously in mouse late embryos and neonates (Hirano et al, 1999;Aoki et al, 2003), although they used an isoform with a shorter cytoplasmic domain lacking the conserved motifs CM-1 and 2, in contrast to the present study in which the longer isoform was examined. Our preliminary investigations have indicated neither the presence nor absence of the shorter variant of Pcdh10 in zebrafish.…”

Expression of classical cadherins in the cerebellar anlage: Quantitative and functional aspects

“…We took advantage of the fact that trypsinization in the presence of calcium selectively spares (a subset of) classical cadherins (Alattia et al, 2002;Hirano et al, 1999;Shimoyama et al, 1999;Kuch et al, 1997;Kido et al, 1998). To ascertain the reliability of this approach in our hands, we first compared reaggregation of cells trypsinized in the absence of calcium (i.e., cells on which all cell adhesion proteins should have been removed; trypsinized following the TEprotocol) to that of cells trypsinized in the presence of 1 mM calcium (i.e.…”

“…Bozdagi et al, 2004;Bamji, 2005) is thus clearly beyond its reach. In contrast, limitations arising from the fact that the current study is restricted to a subset of the multiple cell-cell and cell-substrate contact-mediating proteins differentially expressed in the cerebellar anlage (e.g., protocadherins, tetraspanins, integrins, ephrins; Hirano et al, 1999;Frank et al, 2005;Rogers et al, 1999;Juenger et al, 2005) may be overcome in the future. Likewise, the issue whether, for example, M-, N-and R-cadherin are all expressed in one homogeneous set of granule cells, or whether there exist, among differentiating granule cells, subsets distinguishable by quantitative differences in their expression of these and/or other cadherins may be approached by fully exploiting the multi-parametric potential of flow cytometry.…”