Abstract
The G protein-coupled receptor (GPR) family critically regulates development and homeostasis of multiple organs. As a member of the GPR adhesion family, Gpr125 (Adgra3) modulates Wnt/PCP signaling and convergent extension in developing zebrafish, but whether it is essential for cochlear development in mammals is unknown. Here, we examined the Gpr125lacZ/+ knock-in mice and show that Gpr125 is dynamically expressed in the developing and mature cochleae. From embryonic day (E) 15.5 to postnatal day (P) 30, Gpr125-β-Gal is consistently expressed in the lesser epithelial ridge and its presumed progenies, the supporting cell subtypes Claudius cells and Hensen’s cells. In contrast, Gpr125-β-Gal is expressed transiently in outer hair cells, epithelial cells in the lateral cochlear wall, interdental cells, and spiral ganglion neurons in the late embryonic and early postnatal cochlea. In situ hybridization for Gpr125 mRNA confirmed Gpr125 expression and validated loss of expression in Gpr125lacZ/lacZ cochleae. Lastly, Gpr125lacZ/+ and Gpr125lacZ/lacZ cochleae displayed no detectable loss or disorganization of either sensory or non-sensory cells in the embryonic and postnatal ages and exhibited normal auditory physiology. Together, our study reveals that Gpr125 is dynamically expressed in multiple cell types in the developing and mature cochlea and is dispensable for cochlear development and hearing.
Highlights
G protein-coupled receptors (GPRs) form one of the largest gene families in the human genomes and serve critical functions across multiple organs (Pickering et al, 2008)
In each turn of Gpr125lacZ/+ cochleae, robust nuclear Gpr125-β-Gal expression was detected in the lesser epithelial ridge (LER) and outer sulcus in the lateral cochlear ductal floor and in the spiral ganglion neurons (SGNs) in the modiolus (Figures 1E–G, Supplementary Figures 1A–D)
We observed a relatively weaker Gpr125-β-Gal signal in the outer sulcus extending to the lower half of the lateral cochlear wall (Figures 1E–G)
Summary
G protein-coupled receptors (GPRs) form one of the largest gene families in the human genomes and serve critical functions across multiple organs (Pickering et al, 2008). Among the five subfamilies of mammalian GPRs, the adhesion family represents the second largest and consists of nine distinct subfamilies and 33 members, 10 of which have defined biological functions (Hamann et al, 2015; Vizurraga et al, 2020). Conditional deletion of Gpr124 in adult mice disrupts the blood–brain barrier in ischemic conditions, underscoring its role in the mature organ (Chang et al, 2017). Another member of the GPR adhesion family, Gpr126, is required for myelination by Schwann cells in
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