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- Title
Lrrn1 Regulates Medial Boundary Formation in the Developing Mouse Organ of Corti.
- Authors
Maunsell, Helen R.; Ellis, Kathryn; Kelley, Matthew W.; Driver, Elizabeth Carroll
- Abstract
One of the most striking aspects of the sensory epithelium of the mammalian cochlea, the organ of Corti (OC), is the presence of precise boundaries between sensory and nonsensory cells at its medial and lateral edges. A particular example of this precision is the single row of inner hair cells (IHCs) and associated supporting cells along the medial (neural) boundary. Despite the regularity of this boundary, the developmental processes and genetic factors that contribute to its specification are poorly understood. In this study we demonstrate that Leucine Rich Repeat Neuronal 1 (Lrrn1), which codes for a singlepass, transmembrane protein, is expressed before the development of the mouse organ of Corti in the row of cells that will form its medial border. Deletion of Lrrn1 in mice of mixed sex leads to disruptions in boundary formation that manifest as ectopic inner hair cells and supporting cells. Genetic and pharmacological manipulations demonstrate that Lrrn1 interacts with the Notch signaling pathway and strongly suggest that Lrrn1 normally acts to enhance Notch signaling across the medial boundary. This interaction is required to promote formation of the row of inner hair cells and suppress the conversion of adjacent nonsensory cells into hair cells and supporting cells. These results identify Lrrn1 as an important regulator of boundary formation and cellular patterning during development of the organ of Corti.
- Subjects
CORTI'S organ; HAIR cells; NOTCH signaling pathway; MORPHOGENESIS; MEMBRANE proteins
- Publication
Journal of Neuroscience, 2023, Vol 43, Issue 29, p5305
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2141-22.2023