Assistant Professor, Department of Developmental & Molecular Biology
Assistant Professor, Department of Genetics
PLANAR CELL POLARITY SIGNALING: A MECHANISM FOR CELLULAR POLARIZATION.
To perform many of their functions, most epithelial cells are polarized within the plane of the epithelium, commonly referred to as epithelial planar cell polarity (PCP). The cellular consequences of PCP signaling range from coordinated organization of cytoskeletal elements in single cells to complex migration of groups of cells. Obvious examples of PCP in vertebrates are the ordered arrangement of scales on fish and hairs of mammalian skin. A less visible example is the arrangement of stereocilia in the inner ear, which is essential for hearing. Furthermore, left-right body asymmetry and the complicated movement of mesenchymal cells during gastrulation (called convergent extension) that leads to the elongation and thinning of the body axis also depend on correct PCP signaling. Aberrant PCP signaling leads to neural tube defects such as Spina bifida and cystic kidneys. PCP signaling is, however, best studied in Drosophila melanogaster, mainly because of the versatility of the fly as model system. In Drosophila, PCP can easily be seen, e.g. looking at the precisely aligned hairs on wing cells. Genetic and molecular studies led to the identification of a signaling network – the non-canonical Wnt pathway – directing PCP establishment. In recent years it has become apparent that the PCP signaling module is highly conserved from insects to ascidians and humans and is one of the most exciting topics of developmental biology today.
Due to the available tools and the possibility to use a combination of genetic and biochemical approaches, Drosophila is ideally suited to further dissect the PCP pathway and define its relationship to the cytoskeleton. My lab is particularly interested in how the Fz-adapter protein Dsh is regulated by phosphorylation. We have identified candidate kinases and a phosphatase in a systematic molecular screen based on RNAi. Current projects further address the functional relevance of these kinases. We also study two additional kinases, Nemo and Rho kinase that have previously been shown to be required for the migration aspect of PCP establishment and – in case of Rock – also for tumor cell migration during cancer progression.
We recently started a different project in collaboration with the Cuervo lab to address the existence of Chaperone mediated autophagy in flies, which would allow to study this process relevant for aging in a genetically tractable model organism. This will bring us closer to our goal to use Drosophila as model system to address fundamental questions that are relevant for development and disease.
Maung, S. M. T., Jenny, A. (2011). Planar Cell Polarity in Drosophila. Edited by Carroll, T. Organogenesis, Organogenesis 7(3) 165-179.
Jenny, A. Planar Cell Polarity in the Drosophila Eye. Edited by Reh, T. and Cagan, R. (2010). Curr. Top. Dev. Bio. 93, 189-227.
Jenny, A., Mlodzik, M. (2006). Planar cell polarity signaling: a common mechanism for cellular polarization. Mt Sinai J Med., 73(5), 738-750.
Yanfeng, W.A., Berhane, H., Mola, M., Singh, J., Jenny, A*, Mlodzik, M.* (2011) Functional dissection of phosphorylation of Disheveled in Drosophila. Dev Biol. 360(1), 132-142.
Jenny, A. (2011). Preparation of adult Drosophila eyes for thin sectioning and microscopic analysis. JoVE, In press.
Mirkovic, I., Gault, W.J., Rahnama, M., Jenny, A., Gaengel, K., Bessette, D., Gottardi, C..J ., Verheyen, E., Mlodzik, M. (2011), Nemo kinase phosphorylates β-catenin to promote ommatidial rotation and connectscore PCP factors to E-cadherin–β-catenin. Nature Struct. Mol. Biol. In press.
Pataki, C., Matusek, T., Kurucz, E., Andó, I., Jenny, A., Mihály, J. (2010) Drosophila Rab23 is a planar cell polarity gene involved in the regulation of wing hair number. Genetics 184, 1051-1065.
Itoh, K., Jenny, A., Mlodzik, M., Sokol, S. (2009) Centrosomal localization of Diversin and its relevance to Wnt signaling. J. Cell Sci. 122, 3791-3798
Suyama, R.*, Jenny, A.*, Curado, S.*, Pellis-van Berkel, W., Ephrussi, A. (2008). The actin binding protein Lasp promotes Oskar accumulation at the posterior pole of the Drosophila embryo. Development 136, 95-105.
Jenny, A*., Mlodzik, M. (2008). Modified vectors for the two-step directional cloning of inverted repeats for RNA interference in Drosophila. Biotechniques, 44(3), 335-339.
Wu, J., Jenny, A., Mirkovic, I., Mlodzik, M. (2008). Frizzled-Dishevelled signaling specificity outcome can be modulated by Diego in Drosophila. Mech. Dev. 125(1-2), 30-42.
Moeller, H., Jenny, A., Schaeffer, HJ., Schwarz-Romond, T., Mlodzik, M., Hammerschmidt, M., Birchmeier, W. (2006). Diversin interacts with Dishevelled to control non-canonical Wnt signaling. PNAS, 103(43),15900-15905.
Klein, TJ., Jenny, A., Djiane, A., Mlodzik, M. (2006). Kinase-dependent and –independent functions of Doubletime/CKIe regulate Wnt/b-catenin and Fz/PCP signaling in Drosophila. Curr. Biol. 16(13), 1337-1343.
Jenny, A.*, Hachet, O.*, Zavorsky, P., Cyrklaff, A., Weston, M.D.W., St Johnston, D., Erdely, M., Ephrussi, A. (2006). A translation-independent role of oskar RNA in early Drosophila oogenesis. Development 133, 2827-2833.
Ciruna, B., Jenny, A., Lee, D., Mlodzik, M., Schier, A. (2006) Planar polarity signalling controls reintegration of dividing neuroepithelial cells during neurulation, Nature 439, 220-224.
Jenny, A., Reynolds-Kenneally, J., Das, G., Burnett, M., Mlodzik, M. (2005). Diego and Prickle regulate Frizzled-planar polarity signaling by competing for Dishevelled binding. Nat. Cell Biol. 7(7), 691-697.
Simons, M., Gloy,J., Ganner, A., Axel, B., Bashkurov, M., Krönig, C., Schermer, B., Benzing, T., Cabello, O., Polok, B., Driever, W., Jenny, A., Mlodzik, M., Obara, T., Walz, G. (2005) Inversin, the nephronophthisis type II gene product, functions as a molecular switch between Wnt signaling pathways. Nat. Genet. 37(5), 537-543.
Das, G., Jenny, A., Klein, T.J., Mlodzik, M. (2004) Diego interacts with Prickle and Strabismus/Van Gogh to localize planar cell polarity complexes. Development 131, 4467-4476.
Jenny, A., Darken, R. S., Wilson, P. A. & Mlodzik, M. (2003). Prickle and Strabismus form a functional complex to generate a correct axis during planar cell polarity signaling. EMBO J. 22, 4409-4420.
Jenny, A.*, Minvielle-Sebastia, L*., Preker, P.J.* and Keller, W. (1996). Sequence similarity between the 73-kilodalton protein of mammalian CPSF and a subunit of yeast polyadenylation factor I. Science 29; 1514-1517.
Jenny, A. and Keller, W. (1995). Cloning of cDNAs encoding the 160 kDa subunit of the bovine cleavage and polyadenylation specificity factor. Nucl. Acids Res. 23, 2629-2635.
Jenny, A., Hauri, H.-P. and Keller, W. (1994). Characterisation of Cleavage and polyadenylation specificity factor and cloning of its 100-kilodalton subunit. Mol. Cell. Biol. 14, 8183-8190.
*co-first authors or co-corresponding authors
More Information About Dr. Andreas Jenny
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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Chanin Building, Room 503A
Bronx, NY 10461