Notch signaling regulates the pattern of auditory hair cell differentiation in mammals

The development of the mammalian cochlea is an example of patterning in the peripheral nervous system. Sensory hair cells and supporting cells in the cochlea differentiate via regional and cell fate specification. The Notch s ignaling components shows both distinct and overlapping expression patterns of Notch1 receptor and its ligands Jagged1 (Jag1) and Jagged2 (Jag2) in th e developing auditory epithelium of the rat. On embryonic day 16 (E16), man y precursor cells within the Kolliker's organ immunostained for the presenc e of both Notch1 and Jag1, while the area of hair cell precursors did not e xpress either Notch1 and Jag1. During initial events of hair cell different iation between E18 and birth, Notch1 and Jag1 expression predominated in su pporting cells and Jag2 in nascent hair cells. Early after birth, Jag2 expr ession decreased in hair cells while the pattern of Notch1 expression now i ncluded both supporting cells and hair cells. We show that the normal patte rn of hair cell differentiation is disrupted by alteration of Notch signali ng. A decrease of either Notch1 or Jag1 expression by antisense oligonucleo tides in cultures of the developing sensory epithelium resulted in an incre ase in the number of hair cells. Our data suggest that the Notch1 signaling pathway is involved in a complex interplay between the consequences of dif ferent ligand-Notch1 combinations during cochlear morphogenesis and the pha ses of hair cell differentiation.