Pioneer neurog1 expressing cells ingress into the otic epithelium and instruct neuronal specification

The inner ear is responsible for our senses of hearing and balance, and is made up of a series of fluid-filled cavities. Sounds, and movements of the head, cause the fluid within these cavities to move. This activates neurons that line the cavities, causing them to increase their firing rates and pass on information about the sounds or head movements to the brain. Damage to these neurons can result in deafness or vertigo. But where do the neurons themselves come from? It is generally assumed that all inner ear neurons develop inside an area of the embryo called the inner ear epithelium. Cells in this region are thought to switch on a gene called neurog1, triggering a series of changes that turn them into inner ear neurons. However, using advanced microscopy techniques in zebrafish embryos, Hoijman, Fargas et al. now show that this is not the whole story. While zebrafish do not have external ears, they do possess fluid-filled structures for balance and hearing that are similar to those of other vertebrates. Zebrafish embryos are also transparent, which means that activation of genes can be visualized directly. By imaging zebrafish embryos in real time, Hoijman, Fargas et al. show that the first cells to switch on neurog1 do so outside the inner ear epithelium. These pioneer cells then migrate into the inner ear epithelium and switch on neurog1 in their new neighbors. A substance called fibroblast growth factor tells the inner ear epithelium to let the pioneers enter, and thereby controls the final number of inner ear neurons. The work of Hoijman, Fargas et al. reveals how coordinated activation of genes and movement of cells gives rise to inner ear neurons. This should provide insights into the mechanisms that generate other types of sensory tissue. In the long term, the advances made in this study may lead to new strategies for repairing damaged sensory nerves.