ReviewRevisiting planar cell polarity in the inner ear
Introduction
Planar cell polarity (PCP) has been studied since the 1980s in invertebrates. In particular, PCP functions in Drosophila to control the specific and uniform orientation of the hair that covers the cuticle of the insects [1], [2]. This signaling pathway is well conserved across species, and one can find manifestations of PCP throughout evolution. Examples of PCP signaling include the alignment of fish scales, feathers on birds, or the hair covering mammalian skin, including humans. In Drosophila wing cells, both core PCP and Fat and Dachsous signaling control the planar orientation of actin-rich hairs perpendicular to the surface of the epithelium and coordinate the orientation of these appendages between every cell within the tissue [3], [4], [5]. We will not address the Fat/Dachsous pathway in this review because little is known about its molecular function in the mammalian cochlear inner ear, but many reviews have been published on the subject in recent years [6], [7], [8].
In mammals, the systematic analysis of the impact of PCP signaling disruption on epithelial function did not begin until 2003 [9], [10]. Since 2003, the role of PCP in many tissues, such as muscle, heart, vessels, bones, or the nervous system, has been investigated [11]. In fact, mutations in PCP genes in the mouse revealed that virtually every tissue is affected by the disruption of PCP signaling, emphasizing the central role of this pathway in vertebrate development and tissue function. What was once regarded as a specific mechanism in invertebrates is becoming a major developmental signaling pathway.
In this review, we highlight parallels between the role of PCP in Drosophila melanogaster and mouse cochlea. In light of some recent findings, we propose a role for basal bodies in mediating kinocilium position and thus planar hair cell polarity.
Section snippets
The cochlear epithelium and PCP signaling: a perfect twosome
Since the above mentioned seminal studies [9], [10], the inner ear, specifically the cochlear epithelium, has been accepted as one of the best models to study—and quantify—multiple aspects of the core PCP signaling in mammals [12], [13]. To better understand the importance of PCP signaling within this highly specialized tissue, one needs to understand the mosaic organization of the epithelial cells within the inner ear.
Looking down on a whole-mount preparation of a postnatal day 0 (P0)/P1 mouse
A comparison of mechanisms between Drosophila and mammalian cochlea
One important aspect of PCP signaling in Drosophila wing cells is that the pathway controls two important mechanisms:
- -
the cytoskeletal dynamics within individual cells that lead to the correct positioning of the actin-rich hair distally (cell autonomously)
- -
the polarized transmission of a signal across a tissue, resulting in the coordination of the orientation of every hair (tissue polarity).
The cilium and PCP: specific to vertebrates
Despite the obvious parallel between the initial formation of the actin-rich trichome on the distal edge of Drosophila wing cells and the actin-rich hair bundle on one edge of the vestibular or cochlear hair cells, one major difference exists: the role of the cilium in ciliated hair cells [29]. Scanning electron microscopy studies of vestibular and cochlear epithelia revealed that in early differentiating hair cells the axoneme of the kinocilium projects initially from the center of the apical
Is there another cell autonomous and apical PCP pathway in HCs?
If additional PCP signaling is involved, the candidate proteins controlling this signaling must comply with a certain number of conditions, similar to those that define core PCP proteins. These conditions include apical and asymmetrical localization and regulation of microtubule dynamics. In invertebrates, studies on asymmetric division in the sensory organ precursor (SOP) of Drosophila are of particular interest because the SOP requires both core PCP signaling and a G-protein dependent
Conclusions
Recent data have challenged our views that a core PCP molecular mechanism, directly inherited from Drosophila epithelium, controls the orientation of hair bundle in hair cells of the mammalian cochlear epithelium. Differences in the localization of core PCP proteins, the existence of apparent new players, and the importance of a cilia-related mechanism all lead to a serious re-examination of these views. As mentioned before, the important role of primary cilia in mammalian cells is in contrast
Acknowledgements
We thank Nathalie Sans and Doris Wu for comments on the manuscript. We acknowledge support from the INSERM grant to M.M., Conseil Regional d’Aquitaine Neurocampus program, La Fondation pour la Recherche Medicale (MM, JE), ANR-08-MNPS-040-01 (MM).
References (94)
The frizzled/stan pathway and planar cell polarity in the Drosophila wing
Current Topics in Developmental Biology
(2012)- et al.
Organising cells into tissues: new roles for cell adhesion molecules in planar cell polarity
Current Opinion in Cell Biology
(2005) - et al.
Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse
Current Biology
(2003) - et al.
Asymmetric localisation of planar polarity proteins: mechanisms and consequences
Seminars in Cell and Developmental Biology
(2009) - et al.
PTK7 regulates myosin II activity to orient planar polarity in the mammalian auditory epithelium
Current Biology
(2012) - et al.
Regulation of planar cell polarity by Smurf ubiquitin ligases
Cell
(2009) - et al.
Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt–receptor complex
Developmental Cell
(2008) - et al.
Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2
Developmental Cell
(2011) Planar polarization of Drosophila and vertebrate epithelia
Current Opinion in Cell Biology
(1997)- et al.
Nonautonomous planar polarity patterning in Drosophila: dishevelled-independent functions of frizzled
Developmental Cell
(2002)
Non-cell-autonomous planar cell polarity propagation in the auditory sensory epithelium of vertebrates
Developmental Biology
Structural development of sensory cells in the ear
Seminars in Cell and Developmental Biology
Planar cell polarity signaling, cilia and polarized ciliary beating
Current Opinion in Cell Biology
Intraflagellar transport: it's not just for cilia anymore
Current Opinion in Cell Biology
The PCP pathway instructs the planar orientation of ciliated cells in the Xenopus larval skin
Current Biology
Microtubules enable the planar cell polarity of airway cilia
Current Biology
Planar cell polarity and cilia
Seminars in Cell and Developmental Biology
Planar cell polarity: coordinating morphogenetic cell behaviors with embryonic polarity
Developmental Cell
The partner of inscuteable/discs-large complex is required to establish planar polarity during asymmetric cell division in Drosophila
Cell
Dare to be different: asymmetric cell division in Drosophila, C. elegans and vertebrates
Current Biology
Mitotic spindle orientation in asymmetric and symmetric cell divisions during animal development
Developmental Cell
PAR proteins regulate microtubule dynamics at the cell cortex in C. elegans
Current Biology
Cortical microtubule contacts position the spindle in C. elegans embryos
Cell
Differential expression of beta tubulin isotypes in the adult gerbil cochlea
Hearing Research
Planar cell polarity in Drosophila
Organogenesis
Principles of planar polarity in animal development
Development
Planar cell polarity signaling: from fly development to human disease
Annual Review of Genetics
Planar cell polarity signaling: the developing cell's compass
Cold Spring Harbor Perspectives in Biology
Planar cell polarity signaling: coordination of cellular orientation across tissues
Wiley Interdisciplinary Reviews Developmental Biology
The roles of the cadherins Fat and Dachsous in planar polarity specification in Drosophila
Developmental Dynamics
Identification of Vangl2 and Scrb1 as planar polarity genes in mammals
Nature
The planar cell polarity pathway in vertebrate development
Developmental Dynamics
Detection of planar polarity proteins in mammalian cochlea
Methods in Molecular Biology
Assessing PCP in the cochlea of mammalian ciliopathy models
Methods in Molecular Biology
Actin filaments, stereocilia, and hair cells: how cells count and measure
Annual Review of Cell Biology
The role of Frizzled3 and Frizzled6 in neural tube closure and in the planar polarity of inner-ear sensory hair cells
Journal of Neuroscience
Asymmetric localization of Vangl2 and Fz3 indicate novel mechanisms for planar cell polarity in mammals
Journal of Neuroscience
PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates
Nature
The novel mouse mutant, chuzhoi, has disruption of Ptk7 protein and exhibits defects in neural tube, heart and lung development and abnormal planar cell polarity in the ear
BMC Developmental Biology
Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure
Nature Cell Biology
Planar cell polarity defects and defective Vangl2 trafficking in mutants for the COPII gene Sec24b
Development
Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease
Nature Genetics
Characterization of a Dchs1 mutant mouse reveals requirements for Dchs1-Fat4 signaling during mammalian development
Development
Frizzled/PCP signalling: a conserved mechanism regulating cell polarity and directed motility
Nature Reviews Genetics
Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation
Development
Asymmetric distribution of prickle-like 2 reveals an early underlying polarization of vestibular sensory epithelia in the inner ear
Journal of Neuroscience
Early development of cochlear hair cell stereociliary surface morphology
Archives of Otorhinolaryngology
Cited by (71)
Deficiency of large tumor suppressor kinase 1 causes congenital hearing loss associated with cochlear abnormalities in mice
2021, Biochemical and Biophysical Research Communications2.23 - Presynaptic Physiology of Cochlear Inner Hair Cells
2020, The Senses: A Comprehensive Reference: Volume 1-7, Second EditionThe Actin Nucleator Cobl Is Critical for Centriolar Positioning, Postnatal Planar Cell Polarity Refinement, and Function of the Cochlea
2018, Cell ReportsCitation Excerpt :Sound-evoked basilar membrane vibrations cause stereociliar deflections and open mechanotransduction channels (Fettiplace and Hackney, 2006). While microtubule-based ciliary structures are indicative of PCP and also the orientation of OHC stereociliar bundles in the cochlea precisely reflects PCP in the tissue (Kelley et al., 2009; Ezan and Montcouquiol, 2013), little is known about PCP effectors and about postnatal processes subsequent to classical embryonic PCP signaling. Stereocilia of OHCs are organized as V-shaped bundles inserted into the cortical actin network, the cuticular plate (Tilney et al., 1980; Kitajiri et al., 2010; Szarama et al., 2012).
Neuron-Specific Deletion of Scrib in Mice Leads to Neuroanatomical and Locomotor Deficits
2022, Frontiers in Genetics