Notch signaling in the development of the inner ear: Lessons from Drosophila

The sensory patches in the ear of a vertebrate can be compared with the mec hanosensory bristles of a fly. This comparison has led to the discovery tha t lateral inhibition mediated by the Notch cell-cell signaling pathway, fir st characterized in Drosophila and crucial for bristle development, also ha s a key role in controlling the pattern of sensory hair cells and supportin g cells in the ear. We review the arguments for considering the sensory pat ches of the vertebrate ear and bristles of the insect to be homologous stru ctures, evolved from a common ancestral mechanosensory organ, and we examin e more closely the role of Notch signaling in each system. Using viral vect ors to misexpress components of the Notch pathway in the chick ear, we show that a simple lateral-inhibition model based on feedback regulation of the Notch ligand Delta is inadequate,for the ear just as it is for the fly bri stle. The Notch ligand Serrate1, expressed in supporting cells in the ear, is regulated by lateral induction, not lateral inhibition; commitment to be come a hair cell is not simply controlled by levels of expression of the No tch ligands Delta1, Serrate1, and Serrate2 in the neighbors of the nascent hair cell; and at least one factor, Numb, capable of blocking reception of lateral inhibition is concentrated in hair cells. These findings reinforce the parallels between the vertebrate ear and the fly bristle and show how s tudy of the insect system can help us understand the vertebrate.