Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates

Ross, Alison; May-Simera, Helen; Eichers, Erica R.; Kai, Masahiro; Hill, Josephine; Jagger, Daniel J.; Leitch, Carmen C.; Chapple, J. Paul; Munro, Peter; Fisher, Shannon; Tan, Perciliz L.; Phillips, Helen M.; Leroux, Michel R.; Henderson, Deborah J.; Murdoch, J.; Copp, Andrew J.; Eliot, MM; Lupski, James R.; Kemp, David T.; Dollfus, Hélène; Tada, Masazumi; Katsanis, Nicholas; Forge, Andrew; Beales, Phil

doi:10.1038/ng1644

Cited by 542 publications

(583 citation statements)

References 30 publications

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“…A central role of cilia in the specification of planar cell polarity emerges from studies of BardetBiedl Syndrome (BBS) proteins, whose loss of function produces defective basal bodies (25) and causes polarity defects in the murine cochlea (26). Interestingly, a dominant genetic interaction between Bbs6 and Vangl2 produces rotated hair bundles in mice, and knockdown of bbs4 expression enhances the gastrulation defects in trilobite mutant zebrafish.…”

Section: Discussionmentioning

confidence: 99%

A two-step mechanism underlies the planar polarization of regenerating sensory hair cells

López‐Schier

Hudspeth²

2006

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

162

216

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The restoration of planar cell polarity is an essential but poorly understood step toward physiological recovery during sensoryorgan regeneration. Investigating this issue in the lateral line of the zebrafish, we found that hair cells regenerate in pairs along a single axis established by the restricted localization and oriented division of their progenitors. By analyzing mutants lacking the planar-polarity determinant Vangl2, we ascertained that the uniaxial production of hair cells and the subsequent orientation of their hair bundles are controlled by distinct pathways, whose combination underlies the establishment of hair-cell orientation during development and regeneration. This mechanism may represent a general principle governing the long-term maintenance of planar cell polarity in remodeling epithelia.auditory system ͉ balance ͉ hearing ͉ lateral line ͉ vestibular system E pithelial cells are polarized along the apicobasal axis and often also perpendicularly to this axis, within the plane of the epithelium. The latter type of cellular organization, termed planar cell polarity, has been studied extensively during development in Drosophila (1, 2). Because the epithelia of adult fruit flies harden and, consequently, cannot undergo repair after mechanical damage or cell death, they are not amenable to studies of the postembryonic recovery of planar cell polarity. In vertebrates, the orientation of the hair bundle that projects from the apical surface of a sensory hair cell represents a striking example of planar cell polarity (3, 4). Because the hair bundle's axis of morphological polarization defines the cell's axis of responsiveness to mechanical stimuli, the senses of hearing and equilibrium rely on the coordinated orientation of hair cells across the sensory epithelium (5, 6).The loss of cochlear hair cells in mammals is irreversible. However, other vertebrates can regenerate hair cells (7-9). In birds, for example, regenerated hair cells appear normal and regain their proper orientation (10-12). The mechanisms that underlie the establishment of hair-cell orientation during development remain poorly understood, however, and those active during hair-cell regeneration are unknown. Direct and continuous observation of hair-cell development and regeneration has not yet been achieved, for live imaging of the ear's mechanosensory epithelium is hampered by the inaccessibility of the cochlea within the skull. Furthermore, the long periods needed by some animals to regenerate hair cells pose severe limitations to analyzing the process continuously. Attempts to monitor cellular behavior in neuromasts after hair-cell ablation in salamanders suffered from the absence of cellular and molecular markers (13), which prevented the unambiguous identification of cellular types and the analysis of the recovery of epithelial architecture upon regeneration. In this study, we used the lateral-line system of the zebrafish to circumvent these limitations and to acquire time-lapse sequences of hair-cell formation and regeneration....

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Section: Discussionmentioning

confidence: 99%

A two-step mechanism underlies the planar polarization of regenerating sensory hair cells

López‐Schier

Hudspeth²

2006

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

162

216

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“…Several recent papers suggest a role for PCP in LR asymmetry (Ross et al, 2005;Antic et al, 2010;Song et al, 2010). Not surprisingly, this has been suggested to be due to the actions of PCP in setting up the positioning of cilia in the node (Okada et al, 2005;Hashimoto et al, 2010).…”

Section: Amplification: Bioelectric Redistribution Of Morphogens Andmentioning

confidence: 99%

Far from solved: A perspective on what we know about early mechanisms of left–right asymmetry

Vandenberg

Levin

2010

Developmental Dynamics

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Consistent laterality is a crucial aspect of embryonic development, physiology, and behavior. While strides have been made in understanding unilaterally expressed genes and the asymmetries of organogenesis, early mechanisms are still poorly understood. One popular model centers on the structure and function of motile cilia and subsequent chiral extracellular fluid flow during gastrulation. Alternative models focus on intracellular roles of the cytoskeleton in driving asymmetries of physiological signals or asymmetric chromatid segregation, at much earlier stages. All three models trace the origin of asymmetry back to the chirality of cytoskeletal organizing centers, but significant controversy exists about how this intracellular chirality is amplified onto cell fields. Analysis of specific predictions of each model and crucial recent data on new mutants suggest that ciliary function may not be a broadly conserved, initiating event in left-right patterning. Many questions about embryonic left-right asymmetry remain open, offering fascinating avenues for further research in cell, developmental, and evolutionary biology. Developmental Dynamics 239:3131-3146,

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“…Interestingly, there is evidence that Disheveled regulates cilia formation in Xenopus by facilitating centriole migration and basal body docking (Park et al, 2008). On the other hand, disruption of cilia function appears to influence planar cell polarity, at least in the inner ears (Ross et al, 2005;Jones et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Planar cell polarity effector gene Fuzzy regulates cilia formation and Hedgehog signal transduction in mouse

Heydeck

Zeng

Liu

2009

Developmental Dynamics

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Precise planar cell polarity (PCP) is critical for the development of multiple organ systems in animals. A group of core-PCP proteins are recognized to play crucial roles in convergent extension and other PCPrelated processes in mammals. However, the functions of another group of PCP-regulating proteins, the PCP-effector proteins, are yet to be fully studied. In this study, the generation and characterization of a mouse mutant for the PCP effector gene Fuzzy (Fuz) is reported. Fuz homozygous mutants are embryonically lethal, with multiple defects including neural tube defects, abnormal dorsal/ventral patterning of the spinal cord, and defective anterior/posterior patterning of the limb buds. Fuz mutants also exhibit abnormal Hedgehog (Hh) signaling and inefficient proteolytic processing of Gli3. Finally, a significant decrease in cilia was found in Fuz homozygous mutants. In conclusion, Fuz plays an important role in cilia formation, Hh signal transduction, and embryonic development in mammals. Developmental Dynamics 238:3035-3042,

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Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates

Cited by 542 publications

References 30 publications

A two-step mechanism underlies the planar polarization of regenerating sensory hair cells

A two-step mechanism underlies the planar polarization of regenerating sensory hair cells

Far from solved: A perspective on what we know about early mechanisms of left–right asymmetry

Planar cell polarity effector gene Fuzzy regulates cilia formation and Hedgehog signal transduction in mouse

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