FIGURE 5.11 • Primary cilium in the kidney tubule is a primary sensor for the fuid fow. Primary cilia in kidney function as sensors for the flow of fluid through the tubules. Deflection of the primary cilium opens the mechanoreceptor calcium channels, which are formed by cystic kidney disease– associated proteins (polycystin-1 and policystin-2). This subsequently initiates the influx of calcium into the cell, releasing additional intracellular calcium from the endoplasmic reticulum. Scanning electron micrograph inset shows primary cilia projecting into the lumen of abnormalities. These include cysts in the pancreas and liver that are accompanied by an enlargement and dilatation of the biliary tree system. Other changes include retinitis pigmentosa (abnormalities of the photoreceptors cells of the retina that cause progressive vision loss), sensorineural hearing loss, diabetes, and learning disabilities. The knowledge of the distribution of primary cilia in the body may help to explain the crucial role of these once-forgotten cellular projections in the normal function of many vital internal organs.
During early embryonic development, nodal cilia containing a 9  0 pattern of microtubules establish the left–right asymmetry of internal organs.
Recent studies suggest that specific primary cilia observed in embryos, despite their 9  0 architectural pattern, are motile and play an important role in early embryonic development by generating the left–right asymmetry of internal organs. During gastrulation, a clockwise rotation of these cilia was observed on the ventral surface of the bilaminar embryonic disc in the area near the primitive node, hence the name nodal cilia. These cilia contain motor proteins (dyneins or kinesins) and are capable of rotational movement in a counterclockwise direction as previously described. Most likely, the absence of the central pairs of microtubules is responsible for such movement, the trajectory of which resembles a full cone in contrast to a half-cone trajectory traceable in the motile 9  2 cilia (Table 5.2).
Movement of nodal cilia in the region known as the the collecting tubule. 27,000. (Courtesy of Dr. C. Craig Tisher.) primitive node generates a leftward, or “nodal” flow. This flow is detected by sensory receptors on the left side of the body, which then initiate signaling mechanisms that differ from those on the right side of the embryo. When nodal cilia are immotile or absent, nodal ﬂow does not occur, leading to random placement of internal body organs. Therefore, primary ciliary dyskinesia (immotile cilia syndrome) often results in situs inversus, a condition in which the position of the heart and abdominal organs are reversed.
The first stage of ciliogenesis includes generation of centrioles.
The first stage of ciliary apparatus formation (ciliogenesis) in differentiating cells involves a generation of multiple centrioles. This process occurs either in the centriolar pathway (by duplication of pairs of existing centrioles, see page 69 in Chapter 2) or more commonly in the acentriolar pathway in which centrioles are formed de novo without involvement of existing centrioles. Both pathways give rise to multiple procentrioles, the immediate precursors of centrioles. Procentrioles mature (elongate) to form centrioles, one for each cilium, and migrate to the apical surface of the cell. After perpendicularly aligning themselves and securing to the apical cell membrane by alar sheets (transitional fibers), centrioles assume the function of basal bodies. The next stage of ciliary apparatus formation involves formation of the remaining basal body– associated structures that include basal feet and striated rootlets. From each of the nine triplets that make up the basal body, a microtubule doublet grows upward by poly
FOLDER 5.2 Clinical Correlation: Primary Ciliary Dyskinesia (Immotile Cilia Syndrome)