Gray Lab

The goal of my lab is the study of the cellular and molecular mechanisms essential for spine development and homeostasis using both mouse and zebrafish model systems. We developed conditional mouse models of (i) idiopathic scoliosis (IS) and intervertebral disc herniation by removing Gpr126/Adgrg6 function in osteochondral progenitors (PLoS Genetics, 2019 and eLife 2021); and (ii) early-onset scoliosis after conditional ablation of Prmt5 function in the same progenitor cell type (Dis Model Mech. 2019). Together these results promote a model of the essential role of cartilaginous tissues and extracellular matrix or ‘matriosome’ for the pathogenesis of idiopathic scoliosis (Bone Research, 2019). We have also been at the forefront of establishing the zebrafish model system for analysis of spine development and disorders including vertebral malformations (Developmental Biology, 2014) and scoliosis (Development Dynamics, 2014, Current Biology 2020). In an effort to promote gene discovery, we established a forward genetic screen in zebrafish which isolated a novel collection of adult viable scoliosis mutants, which are the focus of ongoing studies (Developmental Biology 2020). Thus far, our studies in zebrafish identified common mechanistic roles for scoliosis and hydrocephalus affecting alterations in the physiology of the cerebrospinal fluid (PLOS Genetics, 2018) and established a novel, essential role for a cerebrospinal canal resident protein component, the ‘Reissner fiber’, which regulates spine morphogenesis downstream of disrupted cerebrospinal fluid flow (Current Biology, 2020). We will continue to use a multi-tiered approach, combining zebrafish, mouse, and cell culture models, informed by human genomic studies, with the goal to inform early diagnosis of pediatric/musculoskeletal diseases and provide foundational knowledge of the genes and pathways involved in spine homeostasis.