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About Sickkids
About SickKids

Brian Ciruna, PhD

Research Institute
Head & Senior Scientist
Developmental & Stem Cell Biology

University of Toronto
Professor
Department of Molecular Genetics

Chair Positions
Canada Research Chair
Developmental Genetics and Cell Biology


Phone: 416-813-7654 ext. 302050
Fax: 416-813-5252
Email: ciruna@sickkids.ca

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.

External Funding

  • Natural Sciences and Engineering Research Council of Canada (NSERC)
  • Canadian Institutes of Health Research (CIHR)
  • March of Dimes Foundation

Achievements

  • Ontario Early Researcher Award
  • Canada Research Chair - Tier II
  • Human Frontiers Science Program (HFSP) Career Development Award

Publications

For a complete list of publications, please see PubMed

Curtis CW, Ciruna B. (2017). Understanding idiopathic scoliosis: a new zebrafish school of thoughtTrends in Genetics. Mar;33(3):183-196.

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. 2017 May;6(3).

Grimes DT, Boswell CW, Morante NFC, Henkelman RM, Burdine RD, Ciruna B. (2016) Zebrafish models of idiopathic scoliosis link cerebrospinal fluid flow defects to spine curvatureScience. Jun 10;352(6291):1341-4. 

Lau K, Tao K, Liu H, Wen J, Sturgeon K, Sorfazlian N, Wong M, Lazic S, Burrows J, Li D, Deimling S, Scott I, Ciruna B, Simmons C, Henkelman M, Williams T, Hadjantonakis A, Fernandez-Gonzalez R, Sun Y, Hopyan S. (2015) Anisotropic stress orients remodeling of mammalian limb bud ectodermNature Cell Biology. 17(5): 569-579.

Carvajal-Gonzalez J, Balmer S, Mendoza M, Dussert A, Collu G, Weber U, Ciruna B, Mlodzik M. (2015) The clathrin adapter AP-1 complex and Arf1 regulate planar cell polarity in vivoNature Communications. Apr 7(6): 6751. 

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 diseaseNature 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 asymmetryDevelopmental 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 developmentCell 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 zebrafishDevelopment. 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 diversityPLoS 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 vertebratesHuman 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 morphogenesisDevelopment. 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 proteinCell. 138(5):898-910.

Yin C, Ciruna B, Solnica-Krezel L. (2009) Convergence and extension movements during Vertebrate GastrulationCurrent 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 embryogenesisNature. 450(7167): E1-2.

Wang WH, Liu XY, Gelinas D, Ciruna B, Sun Y. (2007) A fully automated robotic system for microinjection of zebrafish embryosPLoS 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 neurulationNature. 439(7073):220-4