The Notch Ligand Jagged1 Is Required for the Formation, Maintenance, and Survival of Hensen's Cells in the Mouse Cochlea
Abstract
During cochlear development, the Notch ligand JAGGED 1 (JAG1) plays an important role in the specification of the prosensory region, which gives rise to sound-sensing hair cells and neighboring supporting cells (SCs). While JAG1's expression is maintained in SCs through adulthood, the function of JAG1 in SC development is unknown. Here, we demonstrate that JAG1 is essential for the formation and maintenance of Hensen's cells, a highly specialized SC subtype located at the edge of the auditory epithelium. UsingSox2CreERT2/+::Jag1loxP/loxPmice of both genders, we show thatJag1deletion at the onset of differentiation, at embryonic day 14.5, disrupted Hensen's cell formation. Similar loss of Hensen's cells was observed whenJag1was deleted after Hensen's cell formation at postnatal day (P) 0/P1 and fate-mapping analysis revealed that in the absence ofJag1, some Hensen's cells die, but others convert into neighboring Claudius cells. In support of a role for JAG1 in cell survival, genes involved in mitochondrial function and protein synthesis were downregulated in the sensory epithelium of P0 cochlea lackingJag1. Finally, usingFgfr3-iCreERT2::Jag1loxP/loxPmice to deleteJag1at P0, we observed a similar loss of Hensen's cells and found that adultJag1mutant mice have hearing deficits at the low-frequency range.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 30, 2020
- Source ID
- 10.1523/jneurosci.1192-20.2020
Entities
People
- Angelika Doetzlhofer
- Brandon C Cox
- Elena Chrysostomou
- Kaley A. Graves
- Luyi Zhou
- Yuanzhao L. Darcy
Organizations
- National Institute on Deafness and Other Communication Disorders
- Office of Naval Research