Asymmetric Localization of Vangl2 and Fz3 Indicate Novel Mechanisms for Planar Cell Polarity in Mammals

Montcouquiol, Mireille; Sans, Nathalie; Huss, David; Kach, Jacob; Dickman, J. David; Forge, Andrew; Rachel, Rivka A.; Copeland, Neal G.; Jenkins, Nancy A.; Bogani, Debora; Murdoch, J.; Warchol, Mark E.; Wenthold, Robert J.; Kelley, Matthew W.

doi:10.1523/jneurosci.4680-05.2006

Cited by 285 publications

(316 citation statements)

References 35 publications

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“…The rabbit anti-ARL13B (1/2,000) was described previously (76). The rabbit anti-VANGL2 antibody was a gift from Mireille Montcouquiol (University of Bordeaux, Bordeaux, France) (1/1,000) (77). The following antibodies were from Sigma-Aldrich: mouse anti-γ-tubulin (clone GTU-88, 1/1,000 for immunofluorescence, 1/5,000 for Western blots), mouse anti-α-tubulin (1/1,000 for immunofluorescence, 1/10,000 for Western blots), mouse anti-acetylated α-tubulin (1/1,000), and rabbit anti-CEP152 (1/200).…”

Section: Methodsmentioning

confidence: 99%

Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo

Bazzi

Anderson

2014

Proc. Natl. Acad. Sci. U.S.A.

170

194

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Significance Centrioles form the core of centrosomes, which organize cilia and interphase and spindle microtubules in animal cells, but centrosome function has not been defined in mammals in vivo. We show that mouse embryos that lack centrioles and centrosomes survive to midgestation, when they lack primary cilia and cilia-dependent signaling. Despite the absence of centrosomes, bipolar spindle formation, chromosome segregation, cell-cycle profile, and DNA damage response are normal in the mutants. Unlike mutants that lack cilia, most cells in acentriolar embryos activate a p53-dependent apoptotic pathway. The data show that mammalian centrioles promote the efficient and rapid assembly of the mitotic spindle and that a short delay in prometaphase activates a checkpoint that leads to p53-dependent cell death in vivo.

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Section: Methodsmentioning

confidence: 99%

Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo

Bazzi

Anderson

2014

Proc. Natl. Acad. Sci. U.S.A.

170

194

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“…Importantly, within the sensory epithelium of the mouse inner ear, Vangl2 (a flamingo homolog), Fz-3 and Fz-6 proteins are asymmetrically localized within the plane of the epithelium, suggesting that the sub-cellular localization, and perhaps function, of at least some of the core PCP components is conserved in mammals [29,30]. Signaling through the PCP/CE pathway activates alternative downstream elements of Dvl, such as the GTPases Rho, Rac and Cdc42 and the c-Jun N-terminal kinase, JNK [26,27,31].…”

Section: The Non-canonical Pathwaymentioning

confidence: 99%

Molecular regulation of kidney development: is the answer blowing in the Wnt?

2007

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Development of the metanephric kidney is a complicated process regulated by reciprocal signals from the ureteric bud and the metanephric mesenchyme that regulate tubule formation and epithelial branching morphogenesis. Over the past several years, several studies have suggested that Wnt signaling is involved in multiple aspects of normal kidney development as well as injury response and cancer progression. We will review these data here.

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“…Remarkably, stereocilia show an apparently stable and regularly graded increase in length from row to row within the stereociliary bundle, even though their PAB appears to undergo actin treadmilling, at least in transfected hair cells in cultured cochlear explants [19]. To signal properly the stereociliary staircase on each hair cell must adopt a specific orientation relative to anatomical landmarks within the cochlea or vestibular system, a feat accomplished in part through the planar cell polarity pathway [20,21]. The overall length of the stereociliary bundle, commonly scored by measuring the length of the tallest stereocilia within a bundle, varies in a reproducible way according to hair cell type or position.…”

Section: Espins In Hair Cell Stereociliamentioning

confidence: 99%

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

Sekerková

Zheng

Loomis

et al. 2006

Cell. Mol. Life Sci.

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The espins are novel actin-bundling proteins that are produced in multiple isoforms from a single gene. They are present at high concentration in the parallel actin bundle of hair cell stereocilia and are the target of deafness mutations in mice and humans. Espins are also enriched in the microvilli of taste receptor cells, solitary chemoreceptor cells, vomeronasal sensory neurons and Merkel cells, suggesting that espins play important roles in the microvillar projections of vertebrate sensory cells. Espins are potent actin-bundling proteins that are not inhibited by Ca 2+ . In cells, they efficiently elongate parallel actin bundles and, thereby, help determine the steady-state length of microvilli and stereocilia. Espins bind actin monomer via their WH2 domain and can assemble actin bundles in cells. Certain espin isoforms can also bind phosphatidylinositol 4,5-bisphosphate, profilins or SH3 proteins. These biological activities distinguish espins from other actin-bundling proteins and may make them well-suited to sensory cells. KeywordsEspin; actin; hair cell; stereocilia; microvilli; sensory; deafness; taste The stereocilia and microvilli of vertebrate sensory cells and their actinbundling proteinsMany classes of vertebrate sensory cells detect chemical or mechanical stimuli through microvilli or their derivatives, such as stereocilia. These relatively long-lived, fingerlike specializations of the plasma membrane are built around a common cytoskeletal element -the parallel actin bundle (PAB) [1]. PABs consist of tightly packed collections of actin filaments cross-linked by actin-bundling proteins. The filaments are aligned along their longitudinal axis and display a uniform polarity with respect to their preferred ends for actin monomer addition, which in microvilli and stereocilia is positioned at the distal tip. The PAB displays hallmarks of a supramolecular scaffold that determines the placement, dimensions, flexibility and signaling properties of microvilli and stereocilia. Although filopodia also contain a PAB at their core and are believed to sense the local environment, they are considerably more dynamic and differ significantly from microvilli and stereocilia in their molecular composition and biogenesis [2].

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Asymmetric Localization of Vangl2 and Fz3 Indicate Novel Mechanisms for Planar Cell Polarity in Mammals

Abstract: Planar cell polarity (PCP) is a process in which cells

Cited by 285 publications

References 35 publications

Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo

Acentriolar mitosis activates a p53-dependent apoptosis pathway in the mouse embryo

Molecular regulation of kidney development: is the answer blowing in the Wnt?

Espins and the actin cytoskeleton of hair cell stereocilia and sensory cell microvilli

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