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

TL;DR

This study shows that the gene Mybl2 helps control the size and pattern of the cochlea's sensory epithelium during development.

Contribution

The paper reveals a new role for Mybl2 in regulating cochlear boundary formation and sensory domain patterning.

Findings

Mybl2 promotes proliferation in the inner sulcus and limits the sensory domain size via Jag1 regulation.

Loss of Mybl2 leads to increased sensory domain size and ectopic inner hair cell formation.

Progenitor cells in the inner sulcus influence sensory epithelium patterning through MYBL2.

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.

Summary: Mybl2 is a Wnt-regulated transcription factor expressed in the developing inner sulcus domain of the cochlea that influences boundary formation between progenitors and the sensory domain, thereby determining the size of the mature sensory epithelium.

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