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446 THE IMPACT OF THE TG737 MUTATION ON NEURONAL CILIA RETENTION.
  1. D. Mahato1,
  2. J. L. Fuchs2
  1. 1Western University of Health Sciences, College of Osteopathic Medicine of the Pacific, Pomona, CA
  2. 2Department of Biology, University of North Texas, Denton, TX

Abstract

Primary cilia are nonmotile organelles with 9 + 0 microtubules that project from the basal body of the cell. It has been substantiated that the main purpose of motile cilia in mammalian cells is to move fluid or mucus over the cell surface. However, the purpose of primary cilia has remained elusive. Primary cilia are shortened in the kidney tubules of Tg737orpk mice with polycystic kidney disease due to ciliary defects. The product of the Tg737 gene is polaris, which is directly involved in a microtubule-dependent transport process called intraflagellar transport (IFT). Previously, to determine the importance of polaris in the development of neuronal cilia, cilium length and numerical density of cilia were quantitatively assessed in four different brain regions on postnatal days 14 and 31 in Tg737orpk mutant and wild-type mice. We have already shown that progressive postnatal decreases occur in the incidence and length of immunostained neuronal cilia, layer 2 of piriform cortex, claustrum, dentate gyrus of the hippocampus, and ventromedial nucleus of the hypothalamus in mutant compared with wild type. Relative to wild type, mutant cilia were about 39% shorter on P14 and 49% shorter on P31, whereas the percentage of neurons with identified cilia declined by 43% on P14 and 72% on P31. The results indicated that the polaris protein plays a role in the retention of cilia via IFT rather than ciliogenesis. However, it is unclear whether the same pattern of expression occurs in other parts of the CNS; therefore, in this study we examined the olfactory bulb. Throughout adulthood the olfactory bulb continues to receive new neurons from the subventricular layer via the rostral migratory stream, where stem cells enter the bulb through the granular layer (GrL) and migrate radially to differentiate into the internal plexiform layer (IPL). Therefore, certain olfactory regions such as GrL are more stem cell-like than others, such as IPL. A similar study design was used on two different layers of olfactory bulbs, the granular layer and internal plexiform layer. The results are consistent with the previous findings in that the polaris mutation affects maintaince of cilia. Whereas the cilia length was reduced by an average of 15.8% in the GrL, the cilia length in IPL was reduced by an average of 48.4%. The data suggest that even after ciliogenesis, intraflagellar transport is necessary to maintain neuronal cilia. Regional heterogeneity in the effect of this gene mutation on neuronal cilia suggests that the functions of some brain regions might be more compromised than others.

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