Enhanced Preprints

Contributions of mirror-image hair cell orientation to mouse otolith organ and zebrafish neuromast function

  1. Kazuya Ono
  2. Amandine Jarysta
  3. Natasha Hughes
  4. Alma Jukic
  5. Vanessa Chang
  6. Michael R. Deans
  7. Ruth Anne Eatock author has email address
  8. Kathleen Cullen author has email address
  9. Katie Kindt author has email address
  10. Basile Tarchini author has email address
  1. Department of Neurobiology, University of Chicago, Chicago, IL, 60637, USA
  2. The Jackson Laboratory, Bar Harbor, ME 04609, USA
  3. Dept. of Biomedical Engineering, Johns Hopkins University, Baltimore, 21205 MD, USA
  4. Section on Sensory Cell Development and Function, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MA, USA
  5. Department of Neurobiology, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, Utah, USA
  6. Department of Otolaryngology - Head & Neck Surgery, Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, Utah, USA
  7. Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore 21205 MD, USA
  8. Department of Neuroscience, Johns Hopkins University, Baltimore 21205 MD, USA
  9. Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore 21205 MD, USA
  10. Tufts University School of Medicine, Boston, MA 02111, USA

Peer review process

Not revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, public reviews, and a response from the authors (if available).

Read more about eLife’s peer review process.

Editors

  • Reviewing Editor
    Pascal Martin
    Institut Curie, Paris, France
  • Senior Editor
    Andrew King
    University of Oxford, Oxford, United Kingdom

Reviewer #1 (Public Review):

Summary:

The authors aim at dissecting the relationship between hair-cell directional mechanosensation and orientation-linked synaptic selectivity, using mice and the zebrafish. They find that Gpr156 mutant animals homogenize the orientation of hair cells without affecting the selectivity of afferent neurons, suggesting that hair-cell orientation is not the feature that determines synaptic selectivity. Therefore, the process of Emx2-dependent synaptic selectivity bifurcates downstream of Gpr156.

Strengths:

This is an interesting and solid paper. It solves an interesting problem and establishes a framework for the following studies. That is, to ask what are the putative targets of Emx2 that affect synaptic selectivity.
The quality of the data is generally excellent.

Weaknesses:

The feeling is that the advance derived from the results is very limited.

Reviewer #2 (Public Review):

Summary:

The authors inquire in particular whether the receptor Gpr156, which is necessary for hair cells to reverse their polarities in the zebrafish lateral line and mammalian otolith organs downstream of the differential expression of the transcription factor Emx2, also controls the mechanosensitive properties of hair cells and ultimately an animal's behavior. This study thoroughly addresses the issue by analyzing the morphology, electrophysiological responses, and afferent connections of hair cells found in different regions of the mammalian utricle and the Ca2+ responses of lateral line neuromasts in both wild-type animals and gpr156 mutants. Although many features of hair cell function are preserved in the mutants-such as development of the mechanosensory organs and the Emx2-dependent, polarity-specific afferent wiring and synaptic pairing-there are a few key changes. In the zebrafish neuromast, the magnitude of responses of all hair cells to water flow resembles that of the wild-type hair cells that respond to flow arriving from the tail. These responses are larger than those observed in hair cells that are sensitive to flow arriving from the head and resemble effects previously observed in Emx2 mutants. The authors note that this behavior suggests that the Emx2-GPR156 signaling axis also impinges on hair cell mechanotransduction. Although mutant mice exhibit normal posture and balance, they display defects in swimming behavior. Moreover, their vestibulo-ocular reflexes are perturbed. The authors note that the gpr156 mutant is a good model to study the role of opposing hair cell polarity in the vestibular system, for the wiring patterns follow the expression patterns of Emx2, even though hair cells are all of the same polarity. This paper excels at describing the effects of gpr156 perturbation in mouse and zebrafish models and will be of interest to those studying the vestibular system, hair cell polarity, and the role of inner-ear organs in animal behavior.

Strengths:

The study is exceptional in including, not only morphological and immunohistochemical indices of cellular identity but also electrophysiological properties. The mutant hair cells of murine maculæ display essentially normal mechanoelectrical transduction and adaptation-with two or even three kinetic components-as well as normal voltage-activated ionic currents.

  1. Howard Hughes Medical Institute
  2. Wellcome Trust
  3. Max-Planck-Gesellschaft
  4. Knut and Alice Wallenberg Foundation