ZFIN Lab: Ciruna Lab

ZFIN ID: ZDB-LAB-060530-1

Ciruna Lab

PI/Director:	Ciruna, Brian
Contact Person:	Ciruna, Brian
Email:	ciruna@sickkids.ca
URL:
Address:	Program in Developmental & Stem Cell Biology The Hospital for Sick Children 101 College Street MaRS East Tower, Room 11-306 Toronto, Ontario, M5G 1L7 Canada
Country:	Canada
Phone:	(416) 813-7654 x2050
Fax:	(416) 813-5252
Line Designation:	hsc

GENOMIC FEATURES ORIGINATING FROM THIS LAB

Show all 26 genomic features

STATEMENT OF RESEARCH INTERESTS

RESEARCH INTERESTS

-Molecular genetic regulation of embryonic development
-Cell polarity and morphogenesis
-Neurulation and neural tube closure defects
-Zebrafish models of development and disease

RESEARCH ACTIVITIES

We are interested in understanding the molecular and genetic mechanisms that regulate early development, with specific emphasis on the planar cell polarity (PCP) signalling pathway and its role in embryonic morphogenesis.

Correct polarity is essential for normal cellular function. The characteristic apical-basolateral polarity of epithelial cells, for example, is required for directional ion transport and deposition of the basal lamina. In addition, polarity may also exist across the plane of an epithelium or field of cells. In vertebrates, this planar cell polarity (or PCP) instructs polarized cell rearrangements and morphogenetic processes that structure and shape the developing embryo. At neurulation, defects in PCP signalling are thought to cause spina bifida and anencephaly - neural tube closure defects that affect one in every 1000 human births. PCP signalling has also been implicated in skin development, polarization of the inner ear sensory epithelium, cardiac development and cancer. However, little is known about how PCP signals ultimately regulate these important cellular and physiological processes.

We are using the zebrafish as a model organism to investigate the fundamental mechanisms by which cell polarity is established, maintained and interpreted in the course of vertebrate embryonic development. By combining powerful live microscopic imaging capabilities with the genetic and embryological techniques afforded by zebrafish research, we are examining the dynamic regulation of PCP signalling at a sub-cellular level. Furthermore, we are employing forward genetic and candidate gene approaches to screen for novel regulators and modifiers of PCP signalling. We hope to gain insight into how regulation of cell polarity functions in normal development, and how aberrations in PCP signalling contribute to congenital malformations and disease.

LAB MEMBERS

Drinjakovic, Jovana Post-Doc	Borovina, Antonia Graduate Student	Hayes, Madeline Graduate Student
Superina, Simone Graduate Student	Ciruna, Leslie Research Staff	Gelinas, Danielle Research Staff
Hutchinson, Sarah Research Staff	Morley, Angela Research Staff

ZEBRAFISH PUBLICATIONS OF LAB MEMBERS

Valencia-Sama, I., Kee, L., Christopher, G., Ohh, M., Layeghifard, M., Shlien, A., Hayes, M.N., Irwin, M.S. (2023) SHP2 inhibition with TNO155 increases efficacy and overcomes resistance of ALK inhibitors in neuroblastoma. Cancer research communications. 3(12):2608-2622

Bui, C.V., Boswell, C.W., Ciruna, B., Rocheleau, J.V. (2023) Apollo-NADP⁺ reveals in vivo adaptation of NADPH/NADP⁺ metabolism in electrically activated pancreatic β cells. Science advances. 9:eadi8317eadi8317

Ali, R.Q., Meyer-Miner, A., David-Rachel, M., Lee, F.J.H., Wilkins, B.J., Karpen, S.J., Ciruna, B., Ghanekar, A., Kamath, B.M. (2023) Loss of a cilia-associated gene, pkd1l1, causes biliary defects in zebrafish: Implications for Biliary Atresia Splenic Malformation. Disease models & mechanisms. 16(10):

Rebello, D., Wohler, E., Erfani, V., Li, G., Aguilera, A.N., Santiago-Cornier, A., Zhao, S., Hwang, S.W., Steiner, R.D., Zhang, T.J., Gurnett, C.A., Raggio, C., Wu, N., Sobreira, N., Giampietro, P.F., Ciruna, B. (2023) COL11A2 as a candidate gene for vertebral malformations and congenital scoliosis. Human molecular genetics. 32(19):2913-2928

Chen, J., Baxi, K., Lipsitt, A.E., Hensch, N.R., Wang, L., Sreenivas, P., Modi, P., Zhao, X.R., Baudin, A., Robledo, D.G., Bandyopadhyay, A., Sugalski, A., Challa, A.K., Kurmashev, D., Gilbert, A.R., Tomlinson, G.E., Houghton, P., Chen, Y., Hayes, M.N., Chen, E.Y., Libich, D.S., Ignatius, M.S. (2023) Defining function of wild-type and three patient specific TP53 mutations in a zebrafish model of embryonal rhabdomyosarcoma. eLIFE. 12:

Jussila, M., Boswell, C.W., Griffiths, N.W., Pumputis, P.G., Ciruna, B. (2022) Live imaging and conditional disruption of native PCP activity using endogenously tagged zebrafish sfGFP-Vangl2. Nature communications. 13:5598

Meyer-Miner, A., Van Gennip, J.L.M., Henke, K., Harris, M.P., Ciruna, B. (2022) Resolving primary pathomechanisms driving idiopathic-like spinal curvature using a new katnb1 scoliosis model. iScience. 25:105028

Shahzad, U., Taccone, M.S., Kumar, S.A., Okura, H., Krumholtz, S., Ishida, J., Mine, C., Gouveia, K., Edgar, J., Smith, C., Hayes, M., Huang, X., Derry, W.B., Taylor, M., Rutka, J.T. (2020) Modeling human brain tumours in flies, worms, and zebrafish: From proof of principle to novel therapeutic targets. Neuro-Oncology. 23(5):718-731

Tsatskis, Y., Rosenfeld, R., Pearson, J.D., Boswell, C., Qu, Y., Kim, K., Fabian, L., Mohammad, A., Wang, X., Robson, M.I., Krchma, K., Wu, J., Gonçalves, J., Hodzic, D., Wu, S., Potter, D., Pelletier, L., Dunham, W.H., Gingras, A.C., Sun, Y., Meng, J., Godt, D., Schedl, T., Ciruna, B., Choi, K., Perry, J.R.B., Bremner, R., Schirmer, E.C., Brill, J.A., Jurisicova, A., McNeill, H. (2020) The NEMP family supports metazoan fertility and nuclear envelope stiffness. Science advances. 6:eabb4591

Rose, C.D., Pompili, D., Henke, K., Van Gennip, J.L.M., Meyer-Miner, A., Rana, R., Gobron, S., Harris, M.P., Nitz, M., Ciruna, B. (2020) SCO-Spondin Defects and Neuroinflammation Are Conserved Mechanisms Driving Spinal Deformity across Genetic Models of Idiopathic Scoliosis. Current biology : CB. 30(12):2363-2373.e6

Hengel, H., Bosso-Lefèvre, C., Grady, G., Szenker-Ravi, E., Li, H., Pierce, S., Lebigot, É., Tan, T.T., Eio, M.Y., Narayanan, G., Utami, K.H., Yau, M., Handal, N., Deigendesch, W., Keimer, R., Marzouqa, H.M., Gunay-Aygun, M., Muriello, M.J., Verhelst, H., Weckhuysen, S., Mahida, S., Naidu, S., Thomas, T.G., Lim, J.Y., Tan, E.S., Haye, D., Willemsen, M.A.A.P., Oegema, R., Mitchell, W.G., Pierson, T.M., Andrews, M.V., Willing, M.C., Rodan, L.H., Barakat, T.S., van Slegtenhorst, M., Gavrilova, R.H., Martinelli, D., Gilboa, T., Tamim, A.M., Hashem, M.O., AlSayed, M.D., Abdulrahim, M.M., Al-Owain, M., Awaji, A., Mahmoud, A.A.H., Faqeih, E.A., Asmari, A.A., Algain, S.M., Jad, L.A., Aldhalaan, H.M., Helbig, I., Koolen, D.A., Riess, A., Kraegeloh-Mann, I., Bauer, P., Gulsuner, S., Stamberger, H., Ng, A.Y.J., Tang, S., Tohari, S., Keren, B., Schultz-Rogers, L.E., Klee, E.W., Barresi, S., Tartaglia, M., Mor-Shaked, H., Maddirevula, S., Begtrup, A., Telegrafi, A., Pfundt, R., Schüle, R., Ciruna, B., Bonnard, C., Pouladi, M.A., Stewart, J.C., Claridge-Chang, A., Lefeber, D.J., Alkuraya, F.S., Mathuru, A.S., Venkatesh, B., Barycki, J.J., Simpson, M.A., Jamuar, S.S., Schöls, L., Reversade, B. (2020) Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy. Nature communications. 11:595

Yan, C., Brunson, D.C., Tang, Q., Do, D., Iftimia, N.A., Moore, J.C., Hayes, M.N., Welker, A.M., Garcia, E.G., Dubash, T.D., Hong, X., Drapkin, B.J., Myers, D.T., Phat, S., Volorio, A., Marvin, D.L., Ligorio, M., Dershowitz, L., McCarthy, K.M., Karabacak, M.N., Fletcher, J.A., Sgroi, D.C., Iafrate, J.A., Maheswaran, S., Dyson, N.J., Haber, D.A., Rawls, J.F., Langenau, D.M. (2019) Visualizing Engrafted Human Cancer and Therapy Responses in Immunodeficient Zebrafish. Cell. 177(7):1903-1914.e14

Van Gennip, J.L.M., Boswell, C.W., Ciruna, B. (2018) Neuroinflammatory signals drive spinal curve formation in zebrafish models of idiopathic scoliosis. Science advances. 4:eaav1781

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

Ignatius, M.S., Hayes, M.N., Moore, F.E., Tang, Q., Garcia, S.P., Blackburn, P.R., Baxi, K., Wang, L., Jin, A., Ramakrishnan, A., Reeder, S., Chen, Y., Nielsen, G.P., Chen, E.Y., Hasserjian, R.P., Tirode, F., Ekker, S.C., Langenau, D.M. (2018) tp53 deficiency causes a wide tumor spectrum and increases embryonal rhabdomyosarcoma metastasis in zebrafish.. eLIFE. 7:

Hayes, M.N., McCarthy, K., Jin, A., Oliveira, M.L., Iyer, S., Garcia, S.P., Sindiri, S., Gryder, B., Motala, Z., Nielsen, G.P., Borg, J.P., van de Rijn, M., Malkin, D., Khan, J., Ignatius, M.S., Langenau, D.M. (2018) Vangl2/RhoA Signaling Pathway Regulates Stem Cell Self-Renewal Programs and Growth in Rhabdomyosarcoma. Cell Stem Cell. 22:414-427.e6

Ignatius, M.S., Hayes, M.N., Lobbardi, R., Chen, E.Y., McCarthy, K.M., Sreenivas, P., Motala, Z., Durbin, A.D., Molodtsov, A., Reeder, S., Jin, A., Sindiri, S., Beleyea, B.C., Bhere, D., Alexander, M.S., Shah, K., Keller, C., Linardic, C.M., Nielsen, P.G., Malkin, D., Khan, J., Langenau, D.M. (2017) The NOTCH1/SNAIL1/MEF2C Pathway Regulates Growth and Self-Renewal in Embryonal Rhabdomyosarcoma. Cell Reports. 19:2304-2318

Jussila, M., Ciruna, B. (2017) Zebrafish models of non-canonical Wnt/planar cell polarity signalling: fishing for valuable insight into vertebrate polarized cell behavior. Wiley interdisciplinary reviews. Developmental biology. 6(3)

Boswell, C.W., Ciruna, B. (2017) Understanding Idiopathic Scoliosis: A New Zebrafish School of Thought. Trends in genetics : TIG. 33(3):183-196

Tenente, I.M., Hayes, M.N., Ignatius, M.S., McCarthy, K., Yohe, M., Sindiri, S., Gryder, B., Oliveira, M.L., Ramakrishnan, A., Tang, Q., Chen, E.Y., Petur Nielsen, G., Khan, J., Langenau, D.M. (2017) Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma. eLIFE. 6

Hanwell, D., Hutchinson, S.A., Collymore, C., Bruce, A.E., Louis, R., Ghalami, A., Allison, W.T., Ekker, M., Eames, B.F., Childs, S., Kurrasch, D.M., Gerlai, R., Thiele, T., Scott, I., Ciruna, B., Dowling, J.J., McFarlane, S., Huang, P., Wen, X.Y., Akimenko, M.A., Waskiewicz, A.J., Drapeau, P., Babiuk, L.A., Dragon, D., Smida, A., Buret, A.G., O'Grady, E., Wilson, J., Sowden-Plunkett, L., Tropepe, V. (2016) Restrictions on the Importation of Zebrafish into Canada Associated with Spring Viremia of Carp Virus. Zebrafish. 13 Suppl 1:S153-63

Grimes, D.T., Boswell, C.W., Morante, N.F., Henkelman, R.M., Burdine, R.D., Ciruna, B. (2016) Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvature. Science (New York, N.Y.). 352:1341-4

Tang, Q., Moore, J.C., Ignatius, M.S., Tenente, I.M., Hayes, M.N., Garcia, E.G., Torres Yordán, N., Bourque, C., He, S., Blackburn, J.S., Look, A.T., Houvras, Y., Langenau, D.M. (2016) Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish. Nature communications. 7:10358

Ignatius, M.S., Hayes, M., Langenau, D.M. (2016) In Vivo Imaging of Cancer in Zebrafish. Advances in experimental medicine and biology. 916:219-37

Carvajal-Gonzalez, J.M., Balmer, S., Mendoza, M., Dussert, A., Collu, G., Roman, A.C., Weber, U., Ciruna, B., Mlodzik, M. (2015) The clathrin adaptor AP-1 complex and Arf1 regulate planar cell polarity in vivo. Nature communications. 6:6751

Seredick, S., Hutchinson, S.A., Van Ryswyk, L., Talbot, J.C., Eisen, J.S. (2014) Lhx3 and Lhx4 suppress Kolmer-Agduhr interneuron characteristics within zebrafish axial motoneurons. Development (Cambridge, England). 141(20):3900-9

Hayes, M., Gao, X., Yu, L.X., Paria, N., Henkelman, R.M., Wise, C.A., Ciruna, B. (2014) ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease. Nature communications. 5:4777

Superina, S., Borovina, A., and Ciruna, B. (2014) Analysis of maternal-zygotic ugdh mutants reveals divergent roles for HSPGs in vertebrate embryogenesis and provides new insight into the initiation of left-right asymmetry. Developmental Biology. 387(2):154-166

Borovina, A. (2014) Investigating the Relationship Between Cilia and Planar Cell Polarity Signalling During Zebrafish Development. Thesis.

Borovina, A., and Ciruna, B. (2013) IFT88 Plays a Cilia- and PCP-Independent Role in Controlling Oriented Cell Divisions during Vertebrate Embryonic Development. Cell Reports. 5(1):37-43

Pan, Y.A., Freundlich, T., Weissman, T.A., Schoppik, D., Wang, X.C., Zimmerman, S., Ciruna, B., Sanes, J.R., Lichtman, J.W., and Schier, A.F. (2013) Zebrabow: multispectral cell labeling for cell tracing and lineage analysis in zebrafish. Development (Cambridge, England). 140(13):2835

Hayes, M., Naito, M., Daulat, A., Angers, S., and Ciruna, B. (2013) Ptk7 promotes non-canonical Wnt/PCP-mediated morphogenesis and inhibits Wnt/beta-catenin-dependent cell fate decisions during vertebrate development. Development (Cambridge, England). 140(8):1807-1818

Seredick, S., Van Ryswyk, L., Hutchinson, S.A., and Eisen, J.S. (2012) Zebrafish Mnx proteins specify one motoneuron subtype and suppress acquisition of interneuron characteristics. Neural Development. 7(1):35

Hutchinson, S.A., Tooke-Locke, E., Wang, J., Tsai, S., Katz, T., and Trede, N.S. (2012) Tbl3 regulates cell cycle length during zebrafish development. Developmental Biology. 368(2):261-272

Schoenebeck, J.J., Hutchinson, S.A., Byers, A., Beale, H.C., Carrington, B., Faden, D.L., Rimbault, M., Decker, B., Kidd, J.M., Sood, R., Boyko, A.R., Fondon, J.W., Wayne, R.K., Bustamante, C.D., Ciruna, B., and Ostrander, E.A. (2012) Variation of BMP3 Contributes to Dog Breed Skull Diversity. PLoS Genetics. 8(8):e1002849

Persaud, A., Alberts, P., Hayes, M., Guettler, S., Clarke, I., Sicheri, F., Dirks, P., Ciruna, B., and Rotin, D. (2011) Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. The EMBO journal. 30(16):3259-73

Borovina, A., Superina, S., Voskas, D., and Ciruna, B. (2010) Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia. Nature cell biology. 12(4):407-412

Frazer, J.K., Meeker, N.D., Rudner, L., Bradley, D.F., Smith, A.C., Demarest, B., Joshi, D., Locke, E.E., Hutchinson, S.A., Tripp, S., Perkins, S.L., and Trede, N.S. (2009) Heritable T-cell malignancy models established in a zebrafish phenotypic screen. Leukemia. 23(10):1825-1835

Calarco, J.A., Superina, S., O'Hanlon, D., Gabut, M., Raj, B., Pan, Q., Skalska, U., Clarke, L., Gelinas, D., van der Kooy, D., Zhen, M., Ciruna, B., and Blencowe, B.J. (2009) Regulation of vertebrate nervous system alternative splicing and development by an SR-related protein. Cell. 138(5):898-910

Yin, C., Ciruna, B., and Solnica-Krezel, L. (2009) Convergence and extension movements during vertebrate gastrulation. Current topics in developmental biology. 89:163-192

Bennett, J.T., Stickney, H.L., Choi, W.Y., Ciruna, B., Talbot, W.S., and Schier, A.F. (2007) Maternal nodal and zebrafish embryogenesis. Nature. 450(7167):E1-E4

Wang, W., Liu, X., Gelinas, D., Ciruna, B., and Sun, Y. (2007) A fully automated robotic system for microinjection of zebrafish embryos. PLoS One. 2(9):e862

Ciruna, B., Jenny, A., Lee, D., Mlodzik, M., and Schier, A.F. (2006) Planar cell polarity signalling couples cell division and morphogenesis during neurulation. Nature. 439(7073):220-224

Ciruna, B., Weidinger, G., Knaut, H., Thisse, B., Thisse, C., Raz, E., and Schier, A.F. (2002) Production of maternal-zygotic mutant zebrafish by germ-line replacement. Proceedings of the National Academy of Sciences of the United States of America. 99(23):14919-14924