Sonic hedgehog in the developing auditory neurons is required to mediate both neuronal and cochlear development

Authors

• LS Wong
• DK Wu

Abstract

The sound detection apparatus in mammals, the cochlea, is tonotopically organized – with high frequency sounds being processed by sensory hair cells (HCs) at the base while those at the apex response to low frequency tones. This tonotopic map along the cochlea are pre-staged by the timing of HC differentiation during development. Our lab has identified that Sonic hedgehog (Shh), which is expressed in the auditory neurons close to the cochlear apex, plays a crucial role in preventing apical HCs from premature differentiation. Thus, a better understanding of this subpopulation of cells is warranted. To address the spatiotemporal origin of these Shh expressing cells, I performed fate mapping analyses using tamoxifen-inducible ShhCreER mice to mark cells that express Shh at different developmental stages. This lineage study revealed that Shh is turned on in each cohort of nascent post-mitotic auditory neurons and its expression level is downregulated when these neurons mature. This transient presence of Shh represents a specific phase of neuronal developmental in these auditory neurons. Furthermore, Shh encodes a signaling molecule and investigation of SHH receptor, Patched, indicates that Patched is expressed in a group of proliferating neural precursors that are immediately adjacent to Shh-expressing cells. This suggests that Shh has an additional role in regulating the development of succeeding auditory neurons. Overall, this study provides insights into the coordinated effects of Shh in regulating the timing of HC differentiation in the cochlea as well as the formation of sensory neurons in the auditory system.

Scientific Focus Area: Developmental Biology

This page was last updated on Friday, March 26, 2021