Two contrasting roles for Notch activity in chick inner ear development:specification of prosensory patches and lateral inhibition of hair-cell differentiation

TLDR

Lateral inhibition mediated by Notch is thought to generate the mosaic of hair cells and supporting cells in the inner ear, but the effects of the activated Notch protein itself have never been directly tested. The study investigates the role of Notch signalling by transiently overexpressing activated Notch (NICD) in the chick otocyst. The authors used transient overexpression of activated Notch (NICD) in the chick otocyst to probe Notch activity. The experiments revealed that activated Notch inhibits hair‑cell differentiation within existing sensory patches while simultaneously inducing ectopic sensory patches, indicating that Notch first promotes prosensory fate and later mediates lateral inhibition to balance hair cell and supporting cell proportions.

Abstract

Lateral inhibition mediated by Notch is thought to generate the mosaic of hair cells and supporting cells in the inner ear, but the effects of the activated Notch protein itself have never been directly tested. We have explored the role of Notch signalling by transiently overexpressing activated Notch (NICD) in the chick otocyst. We saw two contrasting consequences, depending on the time and site of gene misexpression: (1) inhibition of hair-cell differentiation within a sensory patch; and (2) induction of ectopic sensory patches. We infer that Notch signalling has at least two functions during inner ear development. Initially, Notch activity can drive cells to adopt a prosensory character, defining future sensory patches. Subsequently, Notch signalling within each such patch mediates lateral inhibition, restricting the proportion of cells that differentiate as hair cells so as to generate the fine-grained mixture of hair cells and supporting cells.