Development and Regeneration of the Inner Ear: Coordinating cell cycle and differentiation – Constraining Notch signaling.

Abstract

Generating the correct number and type of cells, in the correct ratio and spatial relationship is required for normal functional development of complex tissues. However, the mechanisms coordinating cell proliferation with growth and differentiation to achieve correct organ size and function remain a poorly understood aspect of embryonic development and postnatal regeneration. In this presentation, I will discuss our work on the molecular basis for the timing of cell cycle exit in the embryonic inner ear, and how this is coordinated with differentiation to produce the correct number of hair cell and supporting cell precursors to build a functional organ of Corti. In the second part of my talk I will discuss the mechanisms that govern cell fate decisions between sensory hair cells and the various supporting cell types in the developing organ of Corti. Specifically, I will focus on the role of Notch‐dependent and Notch‐independent mechanisms governing Hes and Hey gene expression, and their potential role in the maintenance of cell fate during subsequent maturation. Finally, I will discuss the potential role of these developmental processes in the failure of regeneration in the mammalian inner ear.