Cell migration, intercalation and growth regulate mammalian cochlear extension

Development. 2017 Oct 15;144(20):3766-3776. doi: 10.1242/dev.151761. Epub 2017 Sep 4.

Abstract

Developmental remodeling of the sensory epithelium of the cochlea is required for the formation of an elongated, tonotopically organized auditory organ, but the cellular processes that mediate these events are largely unknown. We used both morphological assessments of cellular rearrangements and time-lapse imaging to visualize cochlear remodeling in mouse. Analysis of cell redistribution showed that the cochlea extends through a combination of radial intercalation and cell growth. Live imaging demonstrated that concomitant cellular intercalation results in a brief period of epithelial convergence, although subsequent changes in cell size lead to medial-lateral spreading. Supporting cells, which retain contact with the basement membrane, exhibit biased protrusive activity and directed movement along the axis of extension. By contrast, hair cells lose contact with the basement membrane, but contribute to continued outgrowth through increased cell size. Regulation of cellular protrusions, movement and intercalation within the cochlea all require myosin II. These results establish, for the first time, many of the cellular processes that drive the distribution of sensory cells along the tonotopic axis of the cochlea.

Keywords: Cochlear development; Convergent extension; Inner ear; Live imaging; Mouse; Radial intercalation.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Body Patterning
  • Cell Movement*
  • Cell Proliferation
  • Cell Size
  • Cochlea / embryology*
  • Female
  • Gene Expression Regulation, Developmental*
  • Genotype
  • Hair Cells, Auditory / cytology
  • Homozygote
  • Mammals
  • Mice
  • Myosin Type II / metabolism
  • Organ of Corti / embryology
  • SOXB1 Transcription Factors / genetics
  • Time-Lapse Imaging

Substances

  • Atoh1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • Myosin Type II