A cochlear progenitor pool influences patterning of the mammalian sensory epithelium via MYBL2

Development. 2024 Sep 1;151(17):dev202635. doi: 10.1242/dev.202635. Epub 2024 Sep 10.

Abstract

During embryonic development, Wnt signaling influences both proliferation and sensory formation in the cochlea. How this dual nature of Wnt signaling is coordinated is unknown. In this study, we define a novel role for a Wnt-regulated gene, Mybl2, which was already known to be important for proliferation, in determining the size and patterning of the sensory epithelium in the murine cochlea. Using a quantitative spatial analysis approach and analyzing Mybl2 loss-of-function, we show that Mybl2 promoted proliferation in the inner sulcus domain but limited the size of the sensory domain by influencing their adjoining boundary position via Jag1 regulation during development. Mybl2 loss-of-function simultaneously decreased proliferation in the inner sulcus and increased the size of the sensory domain, resulting in a wider sensory epithelium with ectopic inner hair cell formation during late embryonic stages. These data suggest that progenitor cells in the inner sulcus determine boundary formation and pattern the sensory epithelium via MYBL2.

Keywords: Boundary; Cochlea; Progenitors; Sensory epithelium; Support cells.

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation*
  • Cochlea* / cytology
  • Cochlea* / embryology
  • Cochlea* / metabolism
  • Epithelium / embryology
  • Epithelium / metabolism
  • Gene Expression Regulation, Developmental
  • Hair Cells, Auditory, Inner / cytology
  • Hair Cells, Auditory, Inner / metabolism
  • Jagged-1 Protein* / genetics
  • Jagged-1 Protein* / metabolism
  • Mice
  • Stem Cells* / cytology
  • Stem Cells* / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Wnt Signaling Pathway

Substances

  • Cell Cycle Proteins
  • Jag1 protein, mouse
  • Jagged-1 Protein
  • Trans-Activators
  • Mybl2 protein, mouse