Abstract Animal cells achieve and maintain a typical volume through the regulation of ion channels that control osmotic processes. In metazoans, development of properly proportioned bodies also requires volume regulation to be coordinated amongst cells within tissues and across organs and systems. Although ion channels regulating cell volume have been identified in cells in culture, little is known about the mechanisms that regulate cell volume and coordinate volume control throughout whole tissues in vivo. Our proposed studies will investigate in zebrafish a new and conserved pathway controlling cell volume and integrity in vacuolated cells of the notochord. Using genetic, cell biological, physiological, and quantitative in vivo and ex vivo approaches, we will define the physiological mechanisms regulating fluid transport and cell volume in response to mechanical cues.