Ciliated Neurons Research Articles

Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome.

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized primarily by retinal dystrophy, obesity, polydactyly, renal malformations and learning disabilities. Although five BBS genes have been cloned, the molecular basis of this syndrome remains elusive. Here we show that BBS is probably caused by a defect at the basal body of ciliated cells. We have cloned a new BBS gene, BBS8, which encodes a protein with a prokaryotic domain, pilF, involved in pilus formation and twitching mobility. In one family, a homozygous null BBS8 mutation leads to BBS with randomization of left-right body axis symmetry, a known defect of the nodal cilium. We have also found that BBS8 localizes specifically to ciliated structures, such as the connecting cilium of the retina and columnar epithelial cells in the lung. In cells, BBS8 localizes to centrosomes and basal bodies and interacts with PCM1, a protein probably involved in ciliogenesis. Finally, we demonstrate that all available Caenorhabditis elegans BBS homologues are expressed exclusively in ciliated neurons, and contain regulatory elements for RFX, a transcription factor that modulates the expression of genes associated with ciliogenesis and intraflagellar transport.

Kinesin molecular motors: transport pathways, receptors, and human disease.

Kinesin molecular motor proteins are responsible for many of the major microtubule-dependent transport pathways in neuronal and non-neuronal cells. Elucidating the transport pathways mediated by kinesins, the identity of the cargoes moved, and the nature of the proteins that link kinesin motors to cargoes are areas of intense investigation. Kinesin-II recently was found to be required for transport in motile and nonmotile cilia and flagella where it is essential for proper left-right determination in mammalian development, sensory function in ciliated neurons, and opsin transport and viability in photoreceptors. Thus, these pathways and proteins may be prominent contributors to several human diseases including ciliary dyskinesias, situs inversus, and retinitis pigmentosa. Kinesin-I is needed to move many different types of cargoes in neuronal axons. Two candidates for receptor proteins that attach kinesin-I to vesicular cargoes were recently found. One candidate, sunday driver, is proposed to both link kinesin-I to an unknown vesicular cargo and to bind and organize the mitogen-activated protein kinase components of a c-Jun N-terminal kinase signaling module. A second candidate, amyloid precursor protein, is proposed to link kinesin-I to a different, also unknown, class of axonal vesicles. The finding of a possible functional interaction between kinesin-I and amyloid precursor protein may implicate kinesin-I based transport in the development of Alzheimer's disease.

Sensing of cadmium and copper ions by externally exposed ADL, ASE, and ASH neurons elicits avoidance response in Caenorhabditis elegans.

We developed a quantitative assay for Caenorhabditis elegans avoidance behavior. This was then used to demonstrate that the worm moved away from toxic concentrations of Cd2+ and Cu2+, but not Ni2+, all ions that prevented development from larval to adult stages. Mutants that have structural defects in ciliated neurons (che-2 and osm-3) as well as worms with three laser-operated neurons (ADL, ASE, and ASH), showed no avoidance behavior from Cd2+ and Cu2+. These results suggest that the avoidance from Cd2+ and Cu2+ are mediated through multiple neural pathways including ADL, ASE, and ASH neurons. We hypothesize that the three sensing neurons provide increased accuracy of the sensory response and a survival advantage in the natural environment of the worm.

Immunocytochemical identification of primary olfactory afferents in rainbow trout.

We have used a combination of techniques to analyze the primary olfactory projection in trout: anterograde tract tracing with horseradish peroxidase (HRP) and immunocytochemistry with antisera to olfactory marker protein (OMP) and to keyhole limpet hemocyanin (KLH). HRP labeling and the OMP antiserum revealed a subset of ciliated receptor neurons with a wide dendrite that lacked the protruding knob found on other receptor neurons. The organization of the primary olfactory axons was clearly revealed by antisera to KLH, which reacted with no other neurons. When visualized with anti-KLH, fascicles of olfactory axons penetrated the basal lamina of the olfactory rosette at scattered sites and converged to form the olfactory nerve. Fascicles within the olfactory nerve traveled parallel to the long axis of the nerve until resorted by extensive intermixing as they entered the olfactory bulb. Within the olfactory bulb, most axons terminated in nine discrete terminal fields in the glomerular layer; however, a few olfactory nerve axons projected into the ventral medial telencephalon. Fascicles supplying each terminal field in the glomerular layer followed distinctive trajectories within the olfactory nerve layer. Axons ending in two terminal fields made brush-like terminations rather than the glomerular terminations characteristic of the remaining seven fields. After unilateral olfactory nerve transection, returning olfactory axons reestablished the normal pattern of terminal fields within 14 weeks. It is likely that the organization of afferents in the trout olfactory bulb is similarly well regulated during normal receptor cell replacement.

Development of the olfactory organ in the rainbow fish Nematocentris maccullochi (Atheriniformes, Melanotaeniidae).

The development of the olfactory organ in the rainbow fish, Nematocentris maccullochi, was studied using scanning and transmission electron microscopy; it was compared with the developmental process in other teleosts, especially in the closely related atherinids and cyprinodonts. The formation of the nares parallels that in atherinids, salmonids, cyprinids and heterosomats, but differs from that found in cyprinodonts. Another ontogenetic feature in which the olfactory organs of the rainbow fish and also of atherinids differ from those of cyprinodonts, is the occurrence of transitory kinociliary cells which disappear during the postlarval period. The divergent evolutionary pathways are discussed with reference to experimental investigations. During development, ciliated and microvillous receptor cell types occur. At the primary larval stage ciliated receptor neurons are exclusively present. At a later stage the microvillous type develops and becomes equal in frequency. Thus, the microvillous receptor represents a separate type of olfactory neuron and is not a progenitor of the ciliated receptor cell.

On the cavity receptor organ (X-organ or organ of Bellonci) of Artemia salina (Crustacea: Anostraca)

The cavity receptor organ (previously X-organ or organ of Bellonci) of Artemia salina consists of ciliated neurons whose cilia protrude into a cavity beneath the cuticle. The neuronal dendrites penetrate a giant accompanying cell and epidermal cells before entering the cavity. The cavity beneath the cuticle, the ciliated neurons and the connexion with the medulla terminalis justifies a homologization with the frontal filament organ of cirripeds and the third unit of copepods. The term cavity receptor is suggested for this organ. It is hardly homologous with the second unit of copepods and the organs described for many malacostracans under the names of sensory pore X-organ or organ of Bellonci. The latter organs are very similar to the cavity receptor but have an internal cavity formed by glial cells. The cavity receptor organ was previously considered neurosecretory but in the light of the present knowledge it is rather sensory although a double function cannot be denied.

Electron microscopic observations of the olfactory mucosa of the mole

The olfactory mucosa of the mole has been studied with the electron microscope. Bipolar ciliated neurons, supporting and basal epithelial cells have been recognized and theirultrastructure described. Morphological differences of the various parts of the sensory neurons have been emphasized. The considerable number of organelles observed in supporting cells and the complexity of their free surface suggests a more active role for these cells than their name implies.