The Experts below are selected from a list of 1206 Experts worldwide ranked by ideXlab platform

Robert W. Corbett - One of the best experts on this subject based on the ideXlab platform.

Kirk Mykytyn - One of the best experts on this subject based on the ideXlab platform.

  • arborization of dendrites by developing neocortical neurons is dependent on primary cilia and type 3 adenylyl cyclase
    The Journal of Neuroscience, 2013
    Co-Authors: Sarah M. Guadiana, Kirk Mykytyn, Susan L Semplerowland, Daniel Daroszewski, Irina Madorsky, Joshua J Breunig, Matthew R. Sarkisian
    Abstract:

    The formation of primary cilia is a highly choreographed process that can be disrupted in developing neurons by overexpressing neuromodulatory G-protein-coupled receptors GPCRs or by blocking intraflagellar transport. Here, we examined the effects of overexpressing the ciliary GPCRs, 5HT6 and SSTR3, on cilia structure and the differentiation of neocortical neurons. Neuronal overexpression of 5HT6 and SSTR3 was achieved by electroporating mouse embryo cortex in utero with vectors encoding these receptors. We found that overexpression of ciliary GPCRs in cortical neurons, especially 5HT6, induced the formation of long (>30 μm) and often forked cilia. These changes were associated with increased levels of intraflagellar transport proteins and accelerated ciliogenesis in neonatal neocortex, the induction of which required Kif3a, an anterograde motor critical for cilia protein trafficking and growth. GPCR overexpression also altered the complement of signaling molecules within the cilia. We found that SSTR3 and type III adenylyl cyclase (ACIII), proteins normally enriched in neuronal cilia, were rarely detected in 5HT6-elongated cilia. Intriguingly, the changes in cilia structure were accompanied by changes in neuronal morphology. Specifically, disruption of normal ciliogenesis in developing neocortical neurons, either by overexpressing cilia GPCRs or a dominant-negative form of Kif3a, significantly impaired dendrite outgrowth. Remarkably, coexpression of ACIII with 5HT6 restored ACIII to cilia, normalized cilia structure, and restored dendrite outgrowth, effects that were not observed in neurons coexpressing ACIII and dominant-negative form of Kif3a. Collectively, our data suggest the formation of neuronal dendrites in developing neocortex requires structurally normal cilia enriched with ACIII.

  • Neuronal ciliary signaling in homeostasis and disease
    Cellular and Molecular Life Sciences, 2010
    Co-Authors: Jill A. Green, Kirk Mykytyn
    Abstract:

    Primary cilia are a class of cilia that are typically solitary, immotile appendages present on nearly every mammalian cell type. Primary cilia are believed to perform specialized sensory and signaling functions that are important for normal development and cellular homeostasis. Indeed, primary cilia dysfunction is now linked to numerous human diseases and genetic disorders. Collectively, primary cilia disorders are termed as ciliopathies and present with a wide range of clinical features, including cystic kidney disease, retinal degeneration, obesity, polydactyly, anosmia, intellectual disability, and brain malformations. Although significant progress has been made in elucidating the functions of primary cilia on some cell types, the precise functions of most primary cilia remain unknown. This is particularly true for primary cilia on neurons throughout the mammalian brain. This review will introduce primary cilia and ciliary signaling pathways with a focus on neuronal cilia and their putative functions and roles in human diseases.

  • type iii adenylyl cyclase localizes to primary cilia throughout the adult mouse brain
    The Journal of Comparative Neurology, 2007
    Co-Authors: Georgia A. Bishop, Nicolas F. Berbari, Jacqueline Lewis, Kirk Mykytyn
    Abstract:

    Solitary primary cilia project from nearly every cell type in the human body. These organelles are considered to have important sensory and signaling functions. Although primary cilia have been detected throughout the mammalian brain, their functions are unknown. The study of primary cilia in the brain is constrained by the scarcity of specific markers for these organelles. We previously demonstrated that type III adenylyl cyclase (ACIII) is a marker for primary cilia on neonatal hippocampal neurons in vivo and in vitro. We further showed that ACIII localizes to cilia on cultured glial cells. Here, we report that ACIII is a marker for primary cilia throughout many regions of the adult mouse brain. Furthermore, we report that ACIII localizes to primary cilia on choroid plexus cells and some astrocytes in the brain, which to our knowledge is the first report of a marker for visualizing cilia on glia in vivo. Overall, our data indicate that ACIII is a prominent marker of primary cilia in the brain and will provide an important tool to facilitate further investigations into the functions of these organelles.

  • Hippocampal neurons possess primary cilia in culture.
    Journal of Neuroscience Research, 2007
    Co-Authors: Nicolas F. Berbari, Georgia A. Bishop, Candice C. Askwith, Jacqueline Lewis, Kirk Mykytyn
    Abstract:

    Primary cilia are cellular appendages that provide important sensory functions and defects in primary ciliary signaling have been implicated in the pathophysiology of human diseases and developmental abnormalities. Almost all human cell types possess a primary cilium. Neurons throughout the brain possess primary cilia on which certain receptors localize, suggesting that neurons possess cilia-mediated signaling. However, the functional significance of neuronal cilia is unknown. Although there is a great deal of interest in understanding the functions of neuronal cilia, their study is hampered by the lack of an in vitro model system. We report that the majority of hippocampal neurons cultured from postnatal mice possess primary cilia in vitro. Further, we describe cilia proteins that can be labeled to readily visualize neuronal primary cilia in culture. These findings are the first characterization of neuronal primary cilia in vitro and should greatly facilitate further investigations into the function of these organelles.

Leigh A. Johnson - One of the best experts on this subject based on the ideXlab platform.

  • Transfer of the Western North American Species Gilia splendens to SaltuGilia (Polemoniaceae), and the Taxonomic Affinities of Gilia scopulorum, Gilia stellata, and Gilia yorkii
    Novon: A Journal for Botanical Nomenclature, 2007
    Co-Authors: Leigh A. Johnson
    Abstract:

    Two new combinations, SaltuGilia splen- dens (Douglas ex H. Mason & A. D. Grant) L. A. Johnson and S. splendens subsp. grantii (Brand) L. A. Johnson, are proposed for taxa transferred from Gilia Ruiz & Pavon on the basis of phylogenetic relation- ship. The affinities of G. scopulorum M. E. Jones, G. stellata A. Heller, and G. yorkii Shevock & A. G. Day, three species that have been allied with SaltuGilia V. E. Grant & A. D. Grant when treated as a section of

  • Monophyly and generic relationships of polemoniaceae based on matK Sequences
    American Journal of Botany, 1996
    Co-Authors: Leigh A. Johnson, Joanna L. Schultz, Douglas E. Soltis, Pamela S. Soltis
    Abstract:

    Polemoniaceae are often considered a model family for studying evolutionary processes, yet a reliable phylogeny for the family is only now beginning to emerge. To test the monophyly of this family and to elucidate intergeneric relationships, we employed comparative sequencing of the chloroplast gene matK. Parsimony analysis of matK sequences representing 18 genera of Polemoniaceae and nine families from Asteridae sensu lato places Polemoniaceae apart from Solanaceae near Fouquieriaceae, Ericaceae, Sarraceniaceae, and Diapensiaceae. Both this and a subsequent analysis of 59 species of Polemoniaceae indicate that Cobaea is derived from within Polemoniaceae, rather than being the sister to Polemoniaceae as suggested by some authors. The tropical genera Bonplandia, Cantua, and Cobaea form a clade, and the remaining, primarily temperate genera, excluding AcanthoGilia, form a second monophyletic group. AcanthoGilia is placed ambiguously as sister to either the tropical or temperate groups depending on the location of the root for Polemoniaceae. Within the temperate lineage, Polemonium is sister to three large clades: a well-supported clade comprising Phlox, Gymnosteris, Linanthus, Leptodactylon, and Gilia filiformis; a moderately well-supported clade comprising Allophyllum, Collomia, Navarretia, and several species of Gilia; and a weakly supported clade comprising Eriastrum, Ipomopsis, Langloisia, Loeseliastrum, Loeselia, and several species of Gilia. In addition to revealing the extreme polyphyly of Gilia, this analysis suggests that Ipomopsis and Linanthus are also polyphyletic.

Peter Igarashi - One of the best experts on this subject based on the ideXlab platform.

  • Elucidating the function of primary cilia by conditional gene inactivation.
    Current Opinion in Nephrology and Hypertension, 2005
    Co-Authors: Thomas Hiesberger, Peter Igarashi
    Abstract:

    Purpose of review This review discusses recent experimental approaches to determine the function of primary cilia by conditional inactivation of genes crucial for cilia formation. Recent findings A functional role in the sensing of fluid flow was recently assigned to the primary cilia. This discovery shed light onto how cells sense dynamic fluid movements. Conditional inactivation of primary cilia formation in later ontogenic stages demonstrated the crucial role renal primary cilia play in the control of cell proliferation. Summary Primary cilia can act as flow sensors, transmitting signals by means of calcium influx into the cells. Structures based on primary cilia are also crucial for the function of photoreceptor cells and it can be expected that additional functions of these organelles will be determined in the future. An important experimental approach to elucidate the involvement of primary cilia in other physiological processes is to specifically inactivate genes crucial for formation of primary cilia. Morphological and physiological changes induced by the loss of primary cilia will help determine additional roles primary cilia play in physiology and organ development.

  • Elucidating the function of primary cilia by conditional gene inactivation.
    Current opinion in nephrology and hypertension, 2005
    Co-Authors: Thomas Hiesberger, Peter Igarashi
    Abstract:

    This review discusses recent experimental approaches to determine the function of primary cilia by conditional inactivation of genes crucial for cilia formation. A functional role in the sensing of fluid flow was recently assigned to the primary cilia. This discovery shed light onto how cells sense dynamic fluid movements. Conditional inactivation of primary cilia formation in later ontogenic stages demonstrated the crucial role renal primary cilia play in the control of cell proliferation. Primary cilia can act as flow sensors, transmitting signals by means of calcium influx into the cells. Structures based on primary cilia are also crucial for the function of photoreceptor cells and it can be expected that additional functions of these organelles will be determined in the future. An important experimental approach to elucidate the involvement of primary cilia in other physiological processes is to specifically inactivate genes crucial for formation of primary cilia. Morphological and physiological changes induced by the loss of primary cilia will help determine additional roles primary cilia play in physiology and organ development.

James R. Manhart - One of the best experts on this subject based on the ideXlab platform.