PCP and Wnt pathway components act in parallel during zebrafish mechanosensory hair cell orientation

Cecilia Moens,Hua Li,Thomas Woolley,Joaquin Navajas Acedo,Jay R Unruh,Richard Alexander,Tatjana Piotrowski,Matthew G Voas

doi:10.1038/s41467-019-12005-y

Abstract

Planar cell polarity (PCP) plays crucial roles in developmental processes such as gastrulation, neural tube closure and hearing. Wnt pathway mutants are often classified as PCP mutants due to similarities between their phenotypes. Here, we show that in the zebrafish lateral line, disruptions of the PCP and Wnt pathways have differential effects on hair cell orientations. While mutations in the PCP genes vangl2 and scrib cause random orientations of hair cells, mutations in wnt11f1, gpc4 and fzd7a/b induce hair cells to adopt a concentric pattern. This concentric pattern is not caused by defects in PCP but is due to misaligned support cells. The molecular basis of the support cell defect is unknown but we demonstrate that the PCP and Wnt pathways work in parallel to establish proper hair cell orientation. Consequently, hair cell orientation defects are not solely explained by defects in PCP signaling, and some hair cell phenotypes warrant re-evaluation.

Highlights

Planar cell polarity (PCP) plays crucial roles in developmental processes such as gastrulation, neural tube closure and hearing
Because disruptions of both pathways cause hair cell arrangement defects, Wnt pathway mutants are often classified as PCP mutants
In MZwnt11;vangl[2] double homozygous neuromasts, hair cell orientations are randomized as in vangl[2] mutants, suggesting that PCP signaling is normal in MZwnt[11] mutants (Fig. 2)

Summary

Introduction

Planar cell polarity (PCP) plays crucial roles in developmental processes such as gastrulation, neural tube closure and hearing. We show that in the zebrafish lateral line, disruptions of the PCP and Wnt pathways have differential effects on hair cell orientations. We set out to investigate the role of Wnt signaling in polarizing sensory hair cells. Wnt gradients have been implicated in establishing PCP in the ear[23,24] but due to the inaccessibility of the ear, the study of the function of the PCP and Wnt signaling pathways in coordinating hair cell alignment is challenging to investigate. A more experimentally accessible model to study hair cell orientation is the sensory lateral line system of aquatic vertebrates that detects water movements across the body of the animal[25,26]. The D0 placode gives rise to a third primordium that migrates onto the dorsal side of the trunk, called primD25,34

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Conclusion