Cilia in the choroid plexus: their roles in hydrocephalus and beyond

Cilia are whip-like projections that are widely conserved in eukaryotes and function as a motile propeller and/or sensory platform to detect various extracellular stimuli. In vertebrates, cilia are ubiquitously found in most cells, showing structural and functional diversities depending on the cell type. In this review, we focus on the structure and function of cilia in choroid plexus epithelial cells (CPECs). CPECs form one or two dozen non-motile 9+0 cilia, which display transient acquisition of motility during development. Genetic malfunction of cilia can lead to failure of multiple organs including the brain. Especially, several groups have demonstrated that the defects in CPEC cilia cause the communicating form of hydrocephalus. In order to elucidate the molecular mechanisms underlying the hydrocephalus, we have previously demonstrated that the cilia possess an NPFF receptor for autocrine signaling to regulate transepithelial fluid transport. In this perspective, we also discuss the potential involvement of cilia in the other aspects of choroid plexus functions, such as the regulation of brain development and neuroinflammation

Role of KIFC3 motor protein in Golgi positioning and integration

KIFC3, a microtubule (MT) minus end–directed kinesin superfamily protein, is expressed abundantly and is associated with the Golgi apparatus in adrenocortical cells. We report here that disruption of the kifC3 gene induced fragmentation of the Golgi apparatus when cholesterol was depleted. Analysis of the reassembly process of the Golgi apparatus revealed bidirectional movement of the Golgi fragments in both wild-type and kifC3−/− cells. However, we observed a markedly reduced inwardly directed motility of the Golgi fragments in cholesterol-depleted kifC3−/− cells compared with either cholesterol-depleted wild-type cells or cholesterol-replenished kifC3−/− cells. These results suggest that (a) under the cholesterol-depleted condition, reduced inwardly directed motility of the Golgi apparatus results in the observed Golgi scattering phenotype in kifC3−/− cells, and (b) cholesterol is necessary for the Golgi fragments to attain sufficient inwardly directed motility by MT minus end–directed motors other than KIFC3, such as dynein, in kifC3−/− cells. Furthermore, we showed that Golgi scattering was much more drastic in kifC3−/− cells than in wild-type cells to the exogenous dynamitin expression even in the presence of cholesterol. These results collectively demonstrate that KIFC3 plays a complementary role in Golgi positioning and integration with cytoplasmic dynein

Odontoblast differentiation is regulated by an interplay between primary cilia and the canonical Wnt pathway

Primary cilium is a protruding cellular organelle that has various physiological functions, especially in sensory reception. While an avalanche of reports on primary cilia have been published, the function of primary cilia in dental cells remains to be investigated. In this study, we focused on the function of primary cilia in dentin-producing odontoblasts. Odontoblasts, like most other cell types, possess primary cilia, which disappear upon the knockdown of intraflagellar transport-88. In cilia-depleted cells, the expression of dentin sialoprotein, an odontoblastic marker, was elevated, while the deposition of minerals was slowed. This was recapitulated by the activation of canonical Wnt pathway, also decreased the ratio of ciliated cells. In dental pulp cells, as they differentiated into odontoblasts, the ratio of ciliated cells was increased, whereas the canonical Wnt signaling activity was repressed. Our results collectively underscore the roles of primary cilia in regulating odontoblastic differentiation through canonical Wnt signaling. This study implies the existence of a feedback loop between primary cilia and the canonical Wnt pathway

Histochemical Analysis of Renal Dysplasia with Ureteral Atresia

Unilateral small kidney with ureteral obstruction was discovered in a 74-year-old female cadaver during an anatomical dissection course. In order to elucidate the histogenesis of renal dysplasia, we carried out histochemical and immunohistochemical analyses. On macroscopic view, the kidney was approximately 3 cm in length, 2 cm in width and weighed only 9 g. Although the ureter ran from the renal hilus to the bladder, its width was under 2 mm. The renal parenchyma was extremely thin and there was a large congested vein in the renal sinus. On microscopic examination of the kidney, we observed that numerous developing renal tubules had cytokeratin-positive epithelia, most of which were surrounded by concentric fibrosis. However, we could not detect any structures resembling the collecting duct, renal tubules, renal pelvis, or glomeruli. The concentric mesencymal fibrous tissue surrounding the immature renal tubules contained the smooth muscles that were positive for h-caldesmon. Serial sections of the ureter revealed several small and discontinuous lacunae lined by cuboidal and transitional epithelium, which did not constitute a patent lumen through the bladder. This case is a rare case of renal dysplasia with defect in recanalization of the ureteral bud during the early developmental stage

Difference in charge and spin dynamics in a quantum dot-lead coupled system

We analyze time evolution of charge and spin states in a quantum dot coupled to an electric reservoir. Utilizing high-speed single-electron detection, we focus on dynamics induced by the first-order tunneling. We find that there is a difference between the spin and the charge relaxation: the former appears slower than the latter. The difference depends on the Fermi occupation factor and the spin relaxation becomes slower when the energy level of the quantum dot is lowered. We explain this behavior by a theory which includes the first-order tunneling processes. We conduct detailed comparison of the experiment and the theory with changing the energy of the quantum dot levels, and the theory can reproduce the experimental results.Comment: 4 pages, 4 figure