Regulation of the apical extension morphogenesis tunes the mechanosensory response of microvilliated neurons

PLoS Biol. 2019 Apr 19;17(4):e3000235. doi: 10.1371/journal.pbio.3000235. eCollection 2019 Apr.


Multiple types of microvilliated sensory cells exhibit an apical extension thought to be instrumental in the detection of sensory cues. The investigation of the mechanisms underlying morphogenesis of sensory apparatus is critical to understand the biology of sensation. Most of what we currently know comes from the study of the hair bundle of the inner ear sensory cells, but morphogenesis and function of other sensory microvilliated apical extensions remain poorly understood. We focused on spinal sensory neurons that contact the cerebrospinal fluid (CSF) through the projection of a microvilliated apical process in the central canal, referred to as cerebrospinal fluid-contacting neurons (CSF-cNs). CSF-cNs respond to pH and osmolarity changes as well as mechanical stimuli associated with changes of flow and tail bending. In vivo time-lapse imaging in zebrafish embryos revealed that CSF-cNs are atypical neurons that do not lose their apical attachment and form a ring of actin at the apical junctional complexes (AJCs) that they retain during differentiation. We show that the actin-based protrusions constituting the microvilliated apical extension arise and elongate from this ring of actin, and we identify candidate molecular factors underlying every step of CSF-cN morphogenesis. We demonstrate that Crumbs 1 (Crb1), Myosin 3b (Myo3b), and Espin orchestrate the morphogenesis of CSF-cN apical extension. Using calcium imaging in crb1 and espin mutants, we further show that the size of the apical extension modulates the amplitude of CSF-cN sensory response to bending of the spinal cord. Based on our results, we propose that the apical actin ring could be a common site of initiation of actin-based protrusions in microvilliated sensory cells. Furthermore, our work provides a set of actors underlying actin-based protrusion elongation shared by different sensory cell types and highlights the critical role of the apical extension shape in sensory detection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Differentiation
  • Cell Surface Extensions / physiology
  • Cerebrospinal Fluid / physiology
  • Mechanotransduction, Cellular / physiology*
  • Microvilli / physiology*
  • Morphogenesis / physiology
  • Neurons / physiology
  • Sensory Receptor Cells / physiology*
  • Spinal Cord / metabolism
  • Zebrafish / metabolism


  • Actins

Grants and funding

CW: European Research Council (ERC) Starting Grant ‘Optoloco’ (grant no. 311673) CW: Human Frontier Science Program (HFSP) Research Grant (grant no. RGP063-2018) CW: New York Stem Cell Foundation (NYSCF) Neuroscience Award (grant no. NYSCF-R-NI39) PLB,CW: Agence Nationale pour le Recherche ‘‘Investissements d’avenir’’ ANR-10-IAIHU-06 (Big Brain Theory ICM Program) and ANR-11-INBS-0011 (NeurATRIS: Translational Research Infrastructure for Biotherapies in Neurosciences). Medical Research Foundation (FRM): LD: (grant no. FDT20170437143) and MD: (FRM grant number ECO20170637481. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.