Delta 1 expression during avian hair cell regeneration

Postembryonic production of hair cells, the highly specialized receptors fo r hearing, balance and motion detection, occurs in a precisely controlled m anner in select species, including avians, Notch1, Delta1 and Serrate1 medi ate cell specification in several tissues and species. We examined expressi on of the chicken homologs of these genes in the normal and drug-damaged ch ick inner ear to determine if signaling through this pathway changes during hair cell regeneration. In untreated post-hatch chicks, Delta1 mRNA is abu ndant in a subpopulation of cells in the utricle, which undergoes continual postembryonic hair cell production, but it is absent from all cells in the basilar papilla, which is mitotically quiescent, By 3 days after drug-indu ced hair cell injury, Delta1 expression is highly upregulated in areas of c ell proliferation in both the utricle and basilar papilla, Delta1 mRNA leve ls are elevated in progenitor cells during DNA synthesis and/or gap 2 phase s of the cell cycle and expression is maintained in both daughter cells imm ediately after mitosis, Delta1 expression remains upregulated in cells that differentiate into hair cells and is downregulated in cells that do not ac quire the hair cell fate. Delta1 mRNA levels return to normal by 10 days af ter hair cell injury. Serrate1 is expressed in both hair cells and support cells in the utricle and basilar papilla, and its expression does not chang e during the course of drug-induced hair cell regeneration, In contrast, No tch1 expression, which is limited to support cells in the quiescent epithel ium, is increased in post-M-phase cell pairs during hair cell regeneration. This study provides initial evidence that Delta-Notch signaling may be inv olved in maintaining the correct cell types and patterns during postembryon ic replacement of sensory epithelial cells in the chick inner ear.