Cilia are slender, hair-like organelles that project from the surface of most growth-arrested cells in our body. They consist of a microtubule-based axoneme surrounded by a bilayer lipid membrane that is enriched in specific receptor proteins and ion channels. Some types of cilia are motile and present in many copies per cell (e.g. cilia on epithelial cells lining the airways and oviduct) while others are non-motile and present in only one copy per cell. These cilia are also called primary cilia. Whether motile or not, all types of cilia have important sensory functions. Consequently, defects in the assembly or function of cilia can lead to severe diseases and developmental disorders, such as congenital heart disease, cystic kidney disease, obesity, cancer and cognitive defects.
Research in our group is focused on the following aspects of cilia assembly and function:
- The function of primary cilia in coordination of cellular signaling pathways, including PDGFRα, Hedgehog, Wnt and TGFβ signaling
- The function of primary cilia in regulation of cell polarity, migration, differentiation and growth control
- The function of primary cilia in stem cells and organogenesis during embryonic development, including heart development
- The function of primary cilia in tumorigenesis and cancer
- Molecular mechanisms of intraflagellar transport
- Role of microtubule plus end-tracking proteins in ciliogenesis
Our group is a member of the Nordic Cilia and Centrosome Network (www.nordiccilia.org)
Clement, CA , Ajbro, KD , Koefoed, K, Vestergaard, ML , Veland, IR , Henriques de Jesus, MPR , Pedersen, LB, Benmerah, A , Andersen, CY , Larsen, LA & Christensen, ST (2013) TGF-β Signaling Is Associated with Endocytosis at the Pocket Region of the Primary Cilium. Cell Reports 3 (6): 1806-14.
Veland, IR , Montjean, R, Eley, L , Pedersen, LB , Schwab, A, Goodship, J , Kristiansen, K , Pedersen, SHF , Saunier, S & Christensen, ST (2013) Inversin/Nephrocystin-2 is required for fibroblast polarity and directional cell migration. PLoS One 8 (4).
Clement, DL, Mally, S, Stock, C, Lethan, M, Satir, P, Schwab, A, Pedersen, SF & Christensen, ST (2013) PDGFRα signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2-ERK1/2-p90RSK and AKT signaling pathways. Journal of Cell Science 126 (4): 953-965.
Schou, KB , Andersen, J & Pedersen, LB (2013) A divergent calponin homology (NN–CH) domain defines a novel family: implications for evolution of ciliary IFT complex B proteins. Bioinformatics. http://dx.doi.org/ 10.1093/bioinformatics/btt661.
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Pedersen, LB & Christensen, ST (2012) Regulating intraflagellar transport. Nature Cell Biology, vol 14, no. 9, pp. 904-906.
Pedersen, LB, Schrøder, JM, Satir, P & Christensen, ST (2012) The Ciliary Cytoskeleton. Comprehensive Physiology, vol 2, issue 1, pp. 779-803.
Egeberg, DL, Lethan, M, Manguso, R, Schneider, L, Awan, A, Jørgensen, TS, Byskov, AG, Pedersen LB & Christensen, ST (2012) Primary cilia and aberrant cell signaling in epithelial ovarian cancer. Cilia. 1(1):15.
Schrøder, JM , Larsen, J , Komarova, Y, Akhmanova, A , Thorsteinsson, RI , Grigoriev, I, Manguso, R , Christensen, ST , Pedersen, SHF , Geimer, S & Pedersen, LB (2011) EB1 and EB3 promote cilia biogenesis by several centrosome-related mechanisms. Journal of Cell Science, vol 124, pp. 2539-51.
Satir, P, Pedersen, LB & Christensen, ST (2010) The primary cilium at a glance. Journal of Cell Science, vol 123, no. Pt 4, pp. 499-503.
Schneider, L, Cammer, M, Lehman, J, Nielsen, SK, Guerra, CF, Veland, IR, Stock, C, Hoffmann, EK, Yoder, BK, Schwab, A, Satir, P & Christensen, ST (2010) Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts. Cell Physiol Biochem, vol. 25, pp. 279-292.
Schneider, L , Stock, C-M, Dieterich, P, Jensen, BH , Pedersen, LB , Satir, P, Schwab, A, Christensen, ST & Pedersen, SF (2009) The Na+/H+ exchanger NHE1 is required for directional migration stimulated via PDGFR-alpha in the primary cilium. Journal of Cell Biology, vol 185, no. 1, pp. 163-176.
Clement, CA , Kristensen, SG , Møllgård, K , Pazour, GJ, Yoder, BK , Larsen, LA & Christensen, ST (2009) The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation. Journal of Cell Science, vol 122, no. Pt 17, pp. 3070-3082.
Kiprilov, EN , Awan, A , Desprat, R, Velho, M , Clement, CA , Byskov, AG , Andersen, CY , Satir, P, Bouhassira, EE , Christensen, ST & Hirsch, RE (2008) Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machinery. Journal of Cell Biology, vol 180, no. 5, pp. 897-904.
Christensen, ST , Pedersen, SF , Satir, P, Veland, IR & Schneider, L (2008) Chapter 10: The primary cilium coordinates signaling pathways in cell cycle control and migration during development and tissue repair. Current Topics in Developmental Biology, vol 85, pp. 261-301.
Pedersen, LB & Rosenbaum, JL (2008) Intraflagellar Transport (IFT) Role in Ciliary Assembly, Resorption and Signalling. Current Topics in Developmental Biology, vol 85, pp. 23-61.
Schrøder, JM , Schneider, L , Christensen, ST & Pedersen, LB (2007) EB1 is required for primary cilia assembly in fibroblasts. Current Biology, vol 17, no. 13, pp. 1134-1139.
Christensen, ST & Ott, CM (2007) Cell signaling. A ciliary signaling switch. Science, vol 317, issue 5836, pp. 330-331.
Christensen, ST , Pedersen, LB , Schneider, L & Satir, P (2007), Sensory cilia and integration of signal transduction in human health and disease. Traffic - International Journal of Intracellular Transport, vol 8, no. 2, pp. 97-109.
Satir, P & Christensen, ST (2007), Overview of structure and function of mammalian cilia. Annual Review of Physiology, vol 69, pp. 377-400.
Rompolas, P , Pedersen, LB , Patel-King, R & King, S (2007) Chlamydomonas FAP133 is a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Journal of Cell Science, vol 120, pp. 3653-3665.
Pedersen, LB , Geimer, S & Rosenbaum, JL (2006) Dissecting the molecular mechanisms of intraflagellar transport in Chlamydomonas. Current Biology, vol 16, no. 5, pp. 450-459.
Schneider, L , Clement, CA , Teilmann, SC, Pazour, G , Hofman, K , Satir, P & Christensen, ST (2005) PDGFRαα Signaling Is Regulated through the Primary Cilium in Fibroblasts. Current Biology, vol 15, no. 20, pp. 1861-1866.
Pedersen, LB , Miller, MS, Geimer, S, Leitch, JM, Rosenbaum, JL & Cole, DG (2005) Chlamydomonas IFT172 is encoded by FLA11, interacts with CrEB1, and regulates IFT at the flagellar tip. Current Biology, vol 15, no. 3, pp. 262-266.