Rearrangements between differentiating hair cells coordinate planar polarity and the establishment of mirror symmetry in lateral-line neuromasts

Abstract

SummaryIn addition to their ubiquitous apical-basal polarity, many epithelia are also polarized along an orthogonal axis, a phenomenon termed planar cell polarity (PCP). In the mammalian inner ear and the zebrafish lateral line, PCP is revealed through the orientation of mechanosensitive hair cells relative to each other and to the body axes. In each neuromast, the receptor organ of the lateral line, hair bundles are arranged in a mirror-symmetrical fashion. Here we show that the establishment of mirror symmetry is preceded by rotational rearrangements between hair-cell pairs, a behavior consistently associated with the division of hair-cell precursors. Time-lapse imaging of trilobite mutants, which lack the core PCP constituent Vang-like protein 2 (Vangl2), shows that their misoriented hair cells correlate with misaligned divisions of hair-cell precursors and an inability to complete rearrangements accurately. Vangl2 is asymmetrically localized in the cells of the neuromast, a configuration required for accurate completion of rearrangements. Manipulation of Vangl2 expression or of Notch signaling results in a uniform hair-cell polarity, indicating that rearrangements refine neuromast polarity with respect to the body axes.

Gene-expression analysis of hair cell regeneration in the zebrafish lateral line

“…Possibly, mantle cells replenish inner support cells that then differentiate into hair cells. Mantle cells have not been shown to differentiate directly into hair cells (37,38). Therefore, both mantle and inner support cells seem to be involved in reestablishing proper neuromast morphology after hair cell death.…”

“…In zebrafish hair cell regeneration occurs via the proliferation and differentiation of inner support cells (5,6,9,37,38), but detailed lineage analyses have not yet been performed, and the stem cell population has not been identified. Mantle cells are good stem cell candidates, because they migrate to form neuromasts on regenerating tail tips and also form postembryonic neuromasts by a process called "stitching."…”

Cellular projections from sensory hair cells form polarity-specific scaffolds during synaptogenesis

“…New hair cells arise throughout a fish's life by mitosis of precursor cells, each of which yields one anteriorly and one posteriorly polarized hair cell (López-Schier and Hudspeth 2006). Two hours after mitosis, the daughter cells undergo a characteristic rearrangement of their somata (Wibowo et al 2011;Mirković et al 2012) before passing through early, intermediate, and late stages of differentiation, defined by their morphology and physiology (Wibowo et al 2011;Kindt et al 2012). By 18 h after mitosis, the hair cells are functionally mature (Fig.…”

Clarin-1 acts as a modulator of mechanotransduction activity and presynaptic ribbon assembly

“…To confirm clarin-1 expression at the ciliary transition zone, 4 dpf neuromasts were immunostained with the transition zone protein Cc2d2a (Fig. 2, F -I;Bachmann-Gagescu et al, 2011;Williams et al, 2011). Partial colocalization was observed between clarin-1 and Cc2d2a, with clarin-1 restricted to the most basal region of the transition zone (Fig.…”