Basal bodies, kinocilia and planar cell polarity

SummaryThe molecular mechanisms by which cilia orientation is coordinated within and between multiciliated cells (MCCs) is not fully understood. By observing the orientation of basal bodies (BB) in MCCs of mouse oviducts, here, we show that Celsr1, a planar cell polarity (PCP) factor involved in tissue polarity regulation, is dispensable for determining BB orientation in individual cells, whereas CAMSAP3, a microtubule minus-end regulator, is critical for this process but not for PCP. MCCs exhibit a characteristic BB orientation and microtubule gradient along the tissue axis, and these intracellular polarities were maintained in the cells lacking Celsr1, although the intercellular coordination of the polarities was partly disrupted. On the other hand, CAMSAP3 regulated the assembly of microtubules interconnecting BBs by localizing at the BBs, and its mutation led to disruption of intracellular coordination of BB orientation, but not affecting PCP factor localization. Thus, both Celsr1 and CAMSAP3 are responsible for BB orientation but in distinct ways; and therefore, their cooperation should be critical for generating functional multiciliated tissues.

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Planar Cell Polarity Defects and Hearing Loss in Sperm-Associated Antigen 6 (Spag6)-Deficient Mice

AJP Cell Physiology ◽

10.1152/ajpcell.00166.2020 ◽

2020 ◽

Author(s):

Xiaofei Li ◽

Daogong Zhang ◽

Lei Xu ◽

Yuechen Han ◽

Wenwen Liu ◽

...

Keyword(s):

Hearing Loss ◽

Inner Ear ◽

Cell Polarity ◽

Planar Cell Polarity ◽

Structural Features ◽

Sensory Cells ◽

Basal Bodies ◽

Cellular Polarity ◽

Central Apparatus ◽

Deficient Mice

Spag6 encodes an axoneme central apparatus protein that is required for normal flagellar and cilia motility. Recent findings suggest that Spag6 also plays a role in ciliogenesis, orientation of cilia basal feet, and planar polarity. Sensory cells of the inner ear display unique structural features that underlie their mechanosensitivity. They represent a distinctive form of cellular polarity, known as planar cell polarity (PCP). However, a role for Spag6 in the inner ear has not yet been explored. In the present study, the function of Spag6 in the inner ear was examined using Spag6-deficient mice. Our results demonstrate hearing loss in the Spag6 mutants, associated with abnormalities in cellular patterning, cell shape, stereocilia bundles and basal bodies, as well as abnormally distributed Frizzled class receptor 6 (FZD6), suggesting that Spag6 participates in PCP regulation. Moreover, we found that the sub-apical microtubule meshwork was disrupted. Our observations suggest new functions for Spag6 in hearing and PCP in the inner ear.

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Alström Syndrome protein ALMS1 localizes to basal bodies of cochlear hair cells and regulates cilium-dependent planar cell polarity

Human Molecular Genetics ◽

10.1093/hmg/ddq493 ◽

2010 ◽

Vol 20 (3) ◽

pp. 466-481 ◽

Cited By ~ 46

Author(s):

Daniel Jagger ◽

Gayle Collin ◽

John Kelly ◽

Emily Towers ◽

Graham Nevill ◽

...

Keyword(s):

Cell Polarity ◽

Hair Cells ◽

Planar Cell Polarity ◽

Basal Bodies ◽

Cochlear Hair Cells ◽

Alström Syndrome ◽

Alstrom Syndrome ◽

Syndrome Protein

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Planar polarization of cilia in the zebrafish floor-plate involves Par3-mediated posterior localization of highly motile basal bodies

Development ◽

10.1242/dev.196386 ◽

2021 ◽

Author(s):

Antoine Donati ◽

Isabelle Anselme ◽

Sylvie Schneider-Maunoury ◽

Christine Vesque

Keyword(s):

Cell Polarity ◽

Planar Cell Polarity ◽

Apical Cell ◽

Lateral Spreading ◽

Floor Plate ◽

Basal Bodies ◽

Ciliated Epithelium ◽

Pulling Forces ◽

Membrane Contacts ◽

Apical Junctions

Epithelial cilia, whether motile or primary, often display an off-centered planar localization within the apical cell surface. This form of planar cell polarity (PCP) involves the asymmetric positioning of the ciliary basal body (BB). Using the mono-ciliated epithelium of the embryonic zebrafish floor-plate, we investigated the dynamics and mechanisms of BB polarization by live-imaging. BBs were highly motile, making back-and-forth movements along the antero-posterior axis and contacting both the anterior and posterior membranes. Contacts exclusively occurred at junctional Par3 patches and were often preceded by membrane digitations extending towards the BB, suggesting focused cortical pulling forces. Accordingly, BBs and Par3 patches were linked by dynamic microtubules. Later, BBs became less motile and eventually settled at posterior apical junctions enriched in Par3. BB posterior positioning followed Par3 posterior enrichment and was impaired upon Par3 depletion or disorganization of Par3 patches. In the PCP mutant Vangl2, BBs were still motile but displayed poorly-oriented membrane contacts that correlated with Par3 patch fragmentation and lateral spreading. We propose an unexpected function for posterior Par3 enrichment in controlling BB positioning downstream of the PCP pathway.

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Planar polarization of cilia in the zebrafish floor-plate involves Par3-mediated posterior localization of highly motile basal bodies

10.1101/702282 ◽

2019 ◽

Author(s):

Antoine Donati ◽

Sylvie Schneider-Maunoury ◽

Christine Vesque

Keyword(s):

Cell Polarity ◽

Basal Body ◽

Planar Cell Polarity ◽

Floor Plate ◽

Basal Bodies ◽

Ciliated Epithelium ◽

Ciliary Beating ◽

Directional Flow ◽

Pulling Forces ◽

Planar Orientation

ABSTRACTTo produce a directional flow, ciliated epithelia display a uniform orientation of ciliary beating. Oriented beating requires planar cell polarity (PCP), which leads to planar orientation and asymmetric positioning of the ciliary basal body (BB) along the polarity axis. We took advantage of the polarized mono-ciliated epithelium of the embryonic zebrafish floor plate to investigate by live-imaging the dynamics and mechanisms of BB polarization. We showed that BBs, although bearing a cilium, were highly motile along the antero-posterior axis. BBs contacted both the anterior and the posterior membranes, with a bias towards posterior contacts from early somitogenesis on. Contacts exclusively occurred at junctional Par3 local enrichments or “patches” and were often preceded by transient membrane digitations extending towards the BB, suggesting focused cortical pulling forces. Accordingly, BBs and Par3 patches were linked by dynamic microtubules. We showed that Par3 became posteriorly enriched prior to BB posterior positioning and that floor plate polarization was impaired upon Par3 patches disruption triggered by Par3 or aPKC overexpression. In the PCP mutant Vangl2, where floor plate cells fail to polarize, we observed that BB were still motile but presented behavioral defects, such as ectopic contacts with lateral membranes that correlated with Par3 patch fragmentation and spreading to lateral membranes. Our data lead us to propose an unexpected function for posterior local Par3 enrichment in controlling BB asymmetric positioning downstream of the PCP pathway via a microtubule capture/shrinkage mechanism.

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