The Notch Ligand Jagged1 is Required for the Formation, Maintenance, and Survival of Hensen 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 JAG1s 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 cells (HeCs), a highly specialized SC-subtype located at the edge of the auditory epithelium. Deletion of Jag1 at the onset of differentiation, at stage E14.5, disrupted HeC formation. Similar loss of HeCs was observed when Jag1 was deleted at P0/P1 and fate-mapping analysis revealed that in the absence of Jag1 some HeCs 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 P0 cochlea lacking Jag1.