Shaping of inner ear sensory organs through antagonistic interactions between Notch signalling and Lmx1a.

Zoe F Mann,Miso Kang,Héctor Gálvez,Elena Chrysostomou,Elachumee Canden,David Pedreno,Nicolas Daudet,Ziqi Chen,Magdalena Żak

doi:10.7554/elife.33323

Abstract

The mechanisms of formation of the distinct sensory organs of the inner ear and the non-sensory domains that separate them are still unclear. Here, we show that several sensory patches arise by progressive segregation from a common prosensory domain in the embryonic chicken and mouse otocyst. This process is regulated by mutually antagonistic signals: Notch signalling and Lmx1a. Notch-mediated lateral induction promotes prosensory fate. Some of the early Notch-active cells, however, are normally diverted from this fate and increasing lateral induction produces misshapen or fused sensory organs in the chick. Conversely Lmx1a (or cLmx1b in the chick) allows sensory organ segregation by antagonizing lateral induction and promoting commitment to the non-sensory fate. Our findings highlight the dynamic nature of sensory patch formation and the labile character of the sensory-competent progenitors, which could have facilitated the emergence of new inner ear organs and their functional diversification in the course of evolution.

Highlights

The morphogenesis of tissues with a complex three-dimensional architecture and a variety of specialized cell types requires the coordinated action of mechanisms that specify cell identity and position
We found that Lmx1a is one of the factors required for the attenuation of lateral induction: the absence of Lmx1a results in expanded Jag1+ territories in the Bsd mouse vestibular system, whilst the overexpression of cLmx1b in the chick inner ear reduces Jag1 expression and results in misplaced sensory patch borders
The mechanisms that shape the inner ear sensory organs operate on otic progenitor cells that can remain uncommitted for a relatively long period of time, instructing them to switch their genetic program and differentiate along either a sensory or non-sensory lineage

Summary

Introduction

The morphogenesis of tissues with a complex three-dimensional architecture and a variety of specialized cell types requires the coordinated action of mechanisms that specify cell identity and position. The vertebrate inner ear is a formidable model system in which to investigate these processes (Groves and Fekete, 2012; Alsina and Whitfield, 2017). It hosts multiple specialised sensory organs responsible for hearing in the cochlea, and the perception of head movements and position in the vestibular system. Each sensory organ contains a sensory patch, composed of a regular mosaic of mechanosensory ‘hair’ cells, and their supporting cells In between these sensory patches are nonsensory domains, forming a series of fluid-filled canals and constrictions essential for inner ear function. The auditory cochlea forms a coiled tube that contains

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