A conserved regulation of cell expansion underlies notochord mechanics, spine morphogenesis, and endochondral bone lengthening.

Cell size is a key contributor to tissue morphogenesis . As a notable example, growth plate hypertrophic chondrocytes use cellular biogenesis and disproportionate fluid uptake to expand 10-20 times in size to drive lengthening of endochondral bone . Similarly, notochordal cells expand to one of the largest cell types in the developing embryo to drive axial extension . In zebrafish, the notochord vacuolated cells undergo vacuole fusion to form a single large, fluid-filled vacuole that fills the cytoplasmic space and contributes to vacuolated cell expansion . When this process goes awry, the notochord lacks sufficient hydrostatic pressure to support vertebral bone deposition resulting in adult spines with misshapen vertebral bones and scoliosis . However, it remains unclear whether endochondral bone and the notochord share common genetic and cellular mechanisms for regulating cell and tissue expansion. Here, we demonstrate that the 5'-inositol phosphatase gene, , regulates notochord expansion, spine morphogenesis, and endochondral bone lengthening in zebrafish. Furthermore, we show that regulates notochord expansion independent of vacuole fusion, thereby genetically decoupling these processes. We demonstrate that -dependent notochord expansion is essential to establish normal mechanical properties of the notochord to facilitate the development of a straight spine. Finally, we find that is also important for endochondral bone lengthening in fish, as has been shown in the human -related endochondral bone disorder, Opsismodysplasia . Overall, this work reveals a conserved mechanism of cell size regulation that influences disparate tissues critical for skeletal development and short-stature disorders.