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

• National Institutes of Health (NIH)
• Canada Foundation for Innovation (CFI)
• Ontario Research Fund (ORF)
• Human Frontiers Science Program (HFSP)
• Terry Fox Foundation (NCIC)
• Natural Sciences and Engineering Research Council of Canada (NSERC)

Publications

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. Proc. Natl. Acad. Sci. 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 BG, Holmyard D, Kulkarni S, Harpal K, Rossant J, Pawson T. (2000). The SH2 tyrosine phosphatase shp2 is required for mammalian limb development. Nat Genet. 24(4),420-3.

Tropepe V, Sibilia M, Ciruna BG, 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. Dev Biol. 208 (1), 166-88.

Ciruna BG, 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.