Abstract
The mammalian organ of Corti is a highly specialized sensory organ of the cochlea with fine-grained pattern that is essential for auditory function. Previous studies show that the Wnt pathway regulates proliferation, promotes medial compartment formation in the cochlea, differentiation of the mechanosensory hair cells and axon guidance of Type II afferent neurons. WNT ligand expressions are highly dynamic throughout development but are insufficient to explain the roles of the Wnt pathway. We address a potential way for how WNTs specify the medial compartment by characterizing the expression of Porcupine (PORCN), an O-acyltransferase that palmitoylates WNT ligands for secretion. We show PORCN expression across embryonic ages (E)12.5 - E14.5, E16.5, and postnatal day (P)1. Our results showed enriched PORCN in the medial domains during early stages of development, indicating that WNTs have a stronger influence on patterning of the medial compartment. PORCN was rapidly downregulated after E14.5, following the onset of sensory cell differentiation; residual expression remained in some hair cells and supporting cells. On E14.5 and E16.5, we also examined the spatial expression of Gsk3β, an inhibitor of canonical Wnt signaling to determine its potential role in radial patterning of the cochlea. Gsk3β was broadly expressed across the radial axis of the epithelium; therefore, unlikely to control WNT-mediated medial specification. In conclusion, the spatial expression of PORCN enriches WNT secretion from the medial domains of the cochlea to influence the specification of cell fates in the medial sensory domain.
Highlights
Wnt ligands are broadly expressed during cochlear development.
PORCN is restricted to the medial domains in early developmental stages.
Wnt medial specification is regulated at the ligand level by PORCN-mediated WNT secretion.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Funding: NIH R21DC016376 and The Jackson Laboratory start-up funds (to VM)
Declarations of interest: none