ZFIN ID: ZDB-LAB-190716-1
Gray Lab
PI/Director: Gray, Ryan
Contact Person: Gray, Ryan
Email: ryan.gray@austin.utexas.edu
URL: http://www.rsg1lab.com
Address: 1400 Barbara Jordan Blvd. Austin, Texas 78723
Country: United States
Phone: 512-495-5052
Line Designation: ut

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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.

Minowa, Ryoko Technical Staff

Wang, Y., Troutwine, B.R., Zhang, H., Gray, R.S. (2021) The axonemal dynein heavy chain 10 gene is essential for monocilia motility and spine alignment in zebrafish. Developmental Biology. 482:82-90
Terhune, E.A., Cuevas, M.T., Monley, A.M., Wethey, C.I., Chen, X., Cattel, M.V., Bayrak, M.N., Bland, M.R., Sutphin, B., Devon Trahan, G., Taylor, M.R.G., Niswander, L.A., Jones, K.L., Baschal, E.E., Antunes, L., Dobbs, M., Gurnett, C., Appel, B., Gray, R., Miller, N.H. (2020) Mutations in KIF7 Implicated in Idiopathic Scoliosis in Humans and Axial Curvatures in Zebrafish. Human Mutation. 42(4):392-407
Gray, R.S., Gonzalez, R., Ackerman, S.D., Minowa, R., Griest, J.F., Bayrak, M.N., Troutwine, B., Canter, S., Monk, K.R., Sepich, D.S., Solnica-Krezel, L. (2020) Postembryonic screen for mutations affecting spine development in zebrafish. Developmental Biology. 471:18-33
Wang, Y., Liu, Z., Yang, G., Gao, Q., Xiao, L., Li, J., Guo, C., Troutwine, B.R., Gray, R.S., Xie, L., Zhang, H. (2020) Coding Variants Coupled With Rapid Modeling in Zebrafish Implicate Dynein Genes, dnaaf1 and zmynd10, as Adolescent Idiopathic Scoliosis Candidate Genes. Frontiers in cell and developmental biology. 8:582255
Bagnat, M., Gray, R.S. (2020) Development of a straight vertebrate body axis. Development (Cambridge, England). 147(21):
Troutwine, B.R., Gontarz, P., Konjikusic, M.J., Minowa, R., Monstad-Rios, A., Sepich, D.S., Kwon, R.Y., Solnica-Krezel, L., Gray, R.S. (2020) The Reissner Fiber Is Highly Dynamic In Vivo and Controls Morphogenesis of the Spine. Current biology : CB. 30(12):2353-2362.e3
Konjikusic, M.J., Yeetong, P., Boswell, C.W., Lee, C., Roberson, E.C., Ittiwut, R., Suphapeetiporn, K., Ciruna, B., Gurnett, C.A., Wallingford, J.B., Shotelersuk, V., Gray, R.S. (2018) Mutations in Kinesin family member 6 reveal specific role in ependymal cell ciliogenesis and human neurological development. PLoS Genetics. 14:e1007817
Haller, G., McCall, K., Jenkitkasemwong, S., Sadler, B., Antunes, L., Nikolov, M., Whittle, J., Upshaw, Z., Shin, J., Baschal, E., Cruchaga, C., Harms, M., Raggio, C., Morcuende, J.A., Giampietro, P., Miller, N.H., Wise, C., Gray, R.S., Solnica-Krezel, L., Knutson, M., Dobbs, M.B., Gurnett, C.A. (2018) A missense variant in SLC39A8 is associated with severe idiopathic scoliosis. Nature communications. 9:4171
Herbert, A.L., Fu, M.M., Drerup, C.M., Gray, R.S., Harty, B.L., Ackerman, S.D., O'Reilly-Pol, T., Johnson, S.L., Nechiporuk, A.V., Barres, B.A., Monk, K.R. (2017) Dynein/dynactin is necessary for anterograde transport of Mbp mRNA in oligodendrocytes and for myelination in vivo.. Proceedings of the National Academy of Sciences of the United States of America. 114:E9153-E9162
Sanchez, N.E., Harty, B.L., O'Reilly-Pol, T., Ackerman, S.D., Herbert, A.L., Holmgren, M., Johnson, S.L., Gray, R.S., Monk, K.R. (2017) Whole Genome Sequencing-Based Mapping and Candidate Identification of Mutations from Fixed Zebrafish Tissue. G3 (Bethesda). 7(10):3415-3425
Buchan, J.G., Gray, R.S., Gansner, J.M., Alvarado, D.M., Burgert, L., Gitlin, J.D., Gurnett, C.A., Goldsmith, M.I. (2014) Kinesin family member 6 (kif6) is necessary for spine development in zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists. 243(12):1646-57
Gray, R.S., Wilm, T.P., Smith, J., Bagnat, M., Dale, R.M., Topczewski, J., Johnson, S.L., and Solnica-Krezel, L. (2014) Loss of col8a1a function during zebrafish embryogenesis results in congenital vertebral malformations. Developmental Biology. 386(1):72-85