Cell Polarity in Development and Evolution
Cell polarity results from the asymmetric distribution of molecular complexes or cellular structures such as the centrioles. Centrioles form the core of the centrosome, the main organizer of the microtubule cytoskeleton in animal cells. Centrioles are also required for assembling cellular cilia, involved among other things in cell signaling and generating fluid flows underlying the establishment of left/right asymmetry and mucus clearance in the airway.
Development of a multicellular organism involves the integration of cell and organism polarities. Our goal is to understand how centrioles are positioned in response to morphogenetic cues.
We are studying multiciliated epithelia involved in generating directional fluid flows, such as the flow of mucus in the airway (mucus clearance) and the flow of cerebrospinal fluid in the brain ventricles. Defects in the orientation of centrioles in these tissues can result in chronic respiratory infections and a severe neurological defect called hydrocephaly.
Our model system is the planarian (Schmidtea mediterranea), a flatworm that relies on a multiciliated epidermis for its locomotion. We want to understand how polarity pathways control the alignment of ciliary beating - which depends on centriole position within the plane of the plasma membrane - along the anteroposterior axis of planarians. We are studying in particular the role played by conserved centriolar proteins we identified, which affect the direction of locomotion of the animals (Fig. 1).
We also want to understand how the positioning of the centrosome is controlled in response to polarity cues, and how it in turn affects embryonic polarity. In this aim, we are developing another species of flatworms, called Macrostomum lignano, as a model system. Early embryonic development in M. lignano involves asymmetric divisions in controlled orientation and thus a control of centrosome position, as it is the case in many asymmetrically dividing stem cells. Cell division plane orientation is also probably linked to the establishment of left-right asymmetry in this species, which thus constitutes a promising experimental system to understand how the centrosome is connected to organism polarities.
Selection of Publications
Rompolas, P., Azimzadeh, J., Marshall, W.F., and King, S.M. (2013). Analysis of ciliary assembly and function in planaria. Methods Enzymol., 525:245-64
Azimzadeh, J., Wong, M.L., Miller Downhour,D., Sánchez Alvarado., A. and Marshall, W.F. (2012). Loss of the centrosome during evolution of planarians. Science, 335(6067):461-3. (Science Express: Jan. 5, 2012)
Faculty of 1000: 2012. F1000.com/13615956.
Comment in Research Highlights, Nature (12 January 2012).
Azimzadeh, J. (2012). What planarians tell us about cilia, centrioles and centrosomes. Méd. Sci., 28, 681-3