Brian Ciruna, PhD
Developmental & Stem Cell Biology
University of Toronto
Department of Molecular Genetics
Canada Research Chair
Developmental Genetics and Cell Biology
Phone: 416-813-7654 ext. 302050
- Molecular genetic regulation of embryonic development
- Cell polarity and morphogenesis
- Neurulation and neural tube closure defects
- Zebrafish models of development and disease
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.
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Canadian Institutes of Health Research (CIHR)
- March of Dimes Foundation
- Ontario Early Researcher Award
- Canada Research Chair - Tier II
- Human Frontiers Science Program (HFSP) Career Development Award
For a complete list of publications, please see PubMed
Hayes M, Gao X, Yu LX, Paria N, Henkelman RM, Wise CA, Ciruna B. (2014) ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease. Nature Communications. Sep 3;5:4777.
Superina S, Borovina A, 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. Mar 15;387(2):154-66.
Borovina A, Ciruna B. (2013) IFT88 plays a cilia- and PCP-independent role in controlling oriented cell divisions during vertebrate embryonic development. Cell Reports. Oct 17;5(1):37-43
Pan YA, Freundlich T, Weissman TA, Schoppik D, Wang XC, Zimmerman S, Ciruna B, Sanes JR, Lichtman JW, Schier AF. (2013) Zebrabow: multispectral cell labeling for cell tracing and lineage analysis in zebrafish. Development. Jul;140(13):2835-46
Hayes M, Naito M, Daulat A, Angers S, Ciruna B. (2013) Ptk7 promotes non-canonical Wnt/PCP-mediated morphogenesis and inhibits Wnt/β-catenin-dependent cell fate decisions during vertebrate development. Development. 140(8):1807-18.
Schoenebeck, JJ, Hutchinson, SA, Byers, A, Beale, HC, Carrington, B, Faden, DL, Rimbault, M, Decker, B, Kidd, JM, Sood, R, Boyko, AR, Fondon, JF, Wayne, RK, Bustamante, CD, Ciruna, B, and Ostrander, EA. (2012) Variation of BMP3 contributes to dog breed skull diversity. PLoS Genetics. Aug 8(8):e1002849
Persaud, A, Alberts, P, Hayes, H, 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. EMBO Journal. 30(16):3259-73.
Miyamoto, T, Poraxinski, S, Wang, H, Borovina, A, Ciruna, B, Shimizu, A, Kajii, T, Kikuchi, A, Furutani-Seiki, M, and Matsuura S. (2011) Insufficiency of BubR1, a mitotic spindle checkpoint regulator, causes impaired ciliogenesis in vertebrates. Human Molecular Genetics. 20(10):2058-70.
Wyngaarden, LA, Vogeli, KM, Ciruna, B, Wells, M, Hadjantonakis, AK, and Hopyan, S. (2010) Oriented cell motility and division underlie early limb bud morphogenesis. Development. 137(15):2551-8.
Borovina A, Superina S, Voskas D, Ciruna, B. (2010) Vangl2 directs the posterior tilting and asymmetric localization of motile primary cilia. Nature Cell Biology. 12(4):407-412.
Calarco JA, 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, Blencowe BJ. (2009) Regulation of vertebrate nervous system alternative splicing and development by an SR-related protein. Cell. 138(5):898-910.
Yin C, Ciruna B, Solnica-Krezel L. (2009) Convergence and Extension Movements during Vertebrate Gastrulation. Current Topics in Developmental Biology. 89: 163-92.
Bennett JT, Stickney HL, Choi W-Y, Ciruna B, Talbot WS, Schier AF. (2007) Maternal Nodal and zebrafish embryogenesis. Nature. 450(7167): E1-2.
Wang WH, Liu XY, Gelinas D, Ciruna B, 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, Schier AF. (2006) Planar cell polarity signalling couples cell division and morphogenesis during neurulation. Nature. 439(7073):220-4
Ciruna B, Weidinger G, Knaut H, Thisse B, Thisse C, Raz E, Schier AF. (2002) Production of maternal-zygotic mutant zebrafish by germ-line replacement. Proceedings of the National Academy of Sciences, USA. 99(23):14919-24.
Ciruna B, Rossant J. (2001). FGF signalling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak. Developmental Cell. 1(1): 37-49.
Saxton TM, Ciruna B, Holmyard D, Kulkarni S, Harpal K, Rossant J, Pawson T. (2000) The SH2 tyrosine phosphatase shp2 is required for mammalian limb development. Nature Genetics. 24(4):420-3.
Tropepe V, Sibilia M, Ciruna B, Rossant J, Wagner EF, van der Kooy D. (1999) Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon. Developmental Biology. 208(1):166-88.
Ciruna B, Schwartz L, Harpal K, Yamaguchi TP, Rossant J. (1997) Chimeric analysis of fibroblast growth factor receptor-1 (Fgfr1) function: a role for FGFR1 in morphogenetic movement through the primitive streak. Development. 124(14):2829-41.