Notch signalling pathway mediates hair cell development in mammalian cochlea

The mammalian cochlea contains an invariant mosaic of sensory hair cells an d non-sensory supporting cells reminiscent of invertebrate structures such as the compound eye in Drosophila melanogaster(1,2). The sensory epithelium in the mammalian cochlea (the organ of Corti) contains four rows of mechan osensory hair cells: a single row of inner hair cells and three rows of out er hair cells. Each hair cell is separated from the next by an interceding supporting cell, forming an invariant and alternating mosaic that extends t he length of the cochlear duct(1). Previous results suggest that determinat ion of cell fates in the cochlear mosaic occurs via inhibitory interactions between adjacent progenitor cells(3-5) (lateral inhibition). Cells populat ing the cochlear epithelium appear to constitute a developmental equivalenc e group in which developing hair cells suppress differentiation in their im mediate neighbours through lateral inhibition(6). These interactions may be mediated through the Notch signalling pathway, a molecular mechanism that is involved in the determination of a variety of cell fates(7-9) Here we sh ow that genes encoding the receptor protein Notch1 and its ligand, lagged 2 , are expressed in alternating cell types in the developing sensory epithel ium. In addition, genetic deletion of Jag2 results in a significant increas e in sensory hair cells, presumably as a result of a decrease in Notch acti vation. These results provide direct evidence for Notch-mediated lateral in hibition in a mammalian system and support a role for Notch in the developm ent of the cochlear mosaic.