The Actin Nucleator Cobl Is Critical for Centriolar Positioning, Postnatal Planar Cell Polarity Refinement, and Function of the Cochlea

Cell Rep. 2018 Aug 28;24(9):2418-2431.e6. doi: 10.1016/j.celrep.2018.07.087.

Abstract

Proper cochlear hair cell array development and sensory apparatus positioning are achieved by planar cell polarity signaling. Effectors executing proper tissue development and maturation programs are largely unknown. We show that the actin nucleator Cobl is an important effector in postnatal refinement and maintenance of planar cell polarity. During the critical time of hearing onset, these polarity defects coincided with reduced F-actin beneath the sensory apparatus and with premature kinocilium retraction. These defects were accompanied by organizational defects of the pericentriolar scaffold that coincided with basal body and centriolar mispositionings. Importantly, the pericentriolar defects observed in Cobl KO mice were demonstrated to be actin polymerization dependent and calcium/calmodulin signaling dependent. Because Cobl KO phenotypes manifested postnatally, planar cell polarity is not solely an important developmental process. The Cobl-dependent planar cell polarity maintenance and refinement processes we describe here seem critical for hearing, as Cobl KO mice show deficient cochlear amplification.

Keywords: PCM; actin-dependent organization of centrioles/basal bodies; cochlear amplification; cortical actin cytoskeleton; cuticular plate; hearing; kinocilium; organ of Corti; postnatal planar cell polarity refinement; stereocilia bundles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Cell Polarity
  • Centrioles / metabolism*
  • Cochlea / metabolism*
  • Mice

Substances

  • Actins