Transcription factor hierarchies underlying the formation of hair cells versus electroreceptors in the lateral line

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Our sense of hearing, and the information we use for balance, results from the movement of tiny "hairs" on specialised sensory "hair cells" in our inner ears, in response to fluid motion within the inner ear caused by vibrations (for sound) and head movement (for balance). We are born with only a few tens of thousands of these hair cells in each ear and they do not regenerate: they can die through ageing, exposure to loud noise, and after treatment with some antibiotics and chemotherapy drugs. Although mammalian hair cells do not regenerate, hair cells in birds, amphibians and fish can, so there is a great deal of interest in understanding the development and regeneration of hair cells in these species. In fish and amphibians, hair cells are found not just inside the inner ear as in mammals, but also on the body surface, collected in tiny sense organs called neuromasts, which are arranged in characteristic lines over the head and body. These "lateral line" hair cells are just like the ones found in the inner ear, but detect local water flow around the animal (rather than fluid flow within the inner ear). The information is used for finding prey and detecting predators, and contributes to e.g. schooling behaviour. Lateral line hair cells develop embryonically from "lateral line placodes": patches of thickened skin on the head. In zebrafish, the model for almost all research on lateral line hair cell development and regeneration, lateral line placodes migrate in lines over the head and trunk, depositing mechanosensory organs in their wake. However, focusing on a single species potentially limits our understanding of how the development of lateral line hair cells is controlled, both because zebrafish may have evolved some species-specific peculiarities, and because this species, like most such modern "teleost" ("bony") fish (and also frogs, the other commonly used aquatic vertebrate lab model), is missing an entire second set of lateral line organs present in most other aquatic vertebrate groups: ampullary organs, which contain electroreceptors that detect the weak electric fields that surround animals in water. Electroreception, a true "sixth sense", is used for finding prey (for example, a shark can detect a flounder buried in the sand by virtue of the weak electric field surrounding it), for orientation (e.g. for long distance migration relative to the earth's magnetic field) and, in some species, for communication. In species with ampullary organs as well as neuromasts, like sharks, "primitive" bony fishes like sturgeons, and aquatic salamanders such as the axolotl, both types of sense organ form from lateral line placodes that elongate (as opposed to migrate) over the head to form ridges, which eventually fragment, with neuromasts forming in the centre of each ridge and ampullary organs forming on the flanks.The experiments in this grant proposal are aimed at understanding the genes important for the formation of hair cells versus electroreceptors, using the sterlet (a sturgeon) as the model system, from which we can obtain thousands of embryos each year. The fresh perspectives gained through this approach will give us a greater understanding of the mechanisms underlying hair cell development and vertebrate sensory cell type diversification.