Review
Revisiting planar cell polarity in the inner ear

https://doi.org/10.1016/j.semcdb.2013.03.012Get rights and content

Highlights

  • We review recent findings on PCP establishment in mammalian cochlea.

  • We revisit the contrast between Drosophila wing epithelium and mammalian cochlear epithelium.

  • Notably, we focus on similarities and differences in the asymmetric distribution of core PCP proteins.

  • We address the conundrum between the kinocilium position and hair bundle orientation in cochlear hair cells.

  • We propose the existence of another cell-autonomous pathway controlling kinocilium positioning in cochlear hair cells.

Abstract

Since the first implication of the core planar cell polarity (PCP) pathway in stereocilia orientation of sensory hair cells in the mammalian cochlea, much has been written about this subject, in terms of understanding how this pathway can shape the mammalian hair cells and using the inner ear as a model system to understand mammalian PCP signaling. However, many conflicting results have arisen, leading to puzzling questions regarding the actual mechanism and roles of core PCP signaling in mammals and invertebrates. In this review, we summarize our current knowledge on the establishment of PCP during inner ear development and revisit the contrast between wing epithelial cells in Drosophila melanogaster and sensory epithelia in the mammalian cochlea. Notably, we focus on similarities and differences in the asymmetric distribution of core PCP proteins in the context of cell autonomous versus non-autonomous role of PCP signaling in the two systems. Additionally, we address the relationship between the kinocilium position and PCP in cochlear hair cells and increasing results suggest an alternate cell autonomous pathway in regulating PCP in sensory hair cells.

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).

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