Associate Professor, Department of Developmental & Molecular Biology
Associate Professor, Department of Genetics
CANONICAL AND NON-CANONICAL WNT SIGNALING: PATTERNING AND CELL POLARIZATION
Wnt/Wingless (Wg) growth factors commonly signal through either the canonical Wnt (Wg)-Frizzled (Fz)/β-catenin pathway or through non-canonical Wnt pathways such as the Wnt/Fz-planar cellular polarity (PCP) pathway, regulating the polarization of cells within the pane of the epithelium. These two pathways are highly conserved between humans, mice , fish and flies.
Canonical Wnt/b-catenin signaling is essential for many aspects of development. For example in vertebrates, it controls the specification of the dorsal-ventral (D-V) embryonic axis, cell proliferation in many tissues, and the maintenance of stem cells and during vascularization. In addition, aberrant canonical Wnt signaling in humans causes cancer. Our lab studies the function of Wnk kinases, for which we have identified a novel role in Wnt signaling in addition to their well known role in the regulation of ion homeostasis in they kidney, where their lack causes hypertension (Gordon syndrome).
Non-canonical Wnt signaling establishes polarity within the plane o an epithelium, commonly referred to as epithelial planar cell polarity (PCP) or tissue polarity and allows a cell to form structures that require not only positional, but also vectorial information. The cellular consequences of PCP signaling range from coordinated organization of cytoskeletal elements in single cells to complex migration of groups of cells. Examples of PCP in vertebrates can be very obvious, as in the ordered arrangement of scales on fish or hairs of mammalian skin. Less visible examples are the cilia of the respiratory tract and oviduct as well as the stereocilia of the sensory epithelium of the organ of Corti in the vertebrate inner ear. Aberrant PCP can lead to left/right asymmetry defects, open neural tubes, deafness and kidney disease.
PCP signaling is, however, best studied in Drosophila melanogaster, mainly because of the versatility of the fly as model system. Genetic and molecular studies in Drosophila led to the identification of a highly conserved signaling network – the non-canonical Wnt/Frizzled-PCP pathway – directing PCP establishment. 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. Our lab is particularly interested in how Rho kinase (Rock) is required for the migration aspect of PCP establishment which will help to understand tumor cell migration.
A FUNCTIONAL APPROACH TO CHAPERONE MEDIATED AUTOPHAGY IN DROSOPHILA
In collaboration with the Cuervo lab at Einstein, we have recently started to explore whether Chaperone Mediated Autophagy (CMA) exists in flies, a form of autophagy that has previously only been described in mammals. During CMA, proteins containing a KFERQ related targeting motif are selectively degraded in lysosomes. This process is important for cellular quality control. as it helps to prevent the formation of protein aggregates in cells that are the cause of certain neurodegenerative diseases. The ability to study CMA in a genetically tractable model organism with a short lifespan will overcome many of the limitations the CMA field currently faces.
It is our goal to use Drosophila as model system to address fundamental questions that are relevant for development and disease in general.
Serysheva, E., Mlodzik, M*., Jenny, A*. (2014). WNKs: An Unexpected Role in Wnt/b-catenin Signaling. Invited Feature Article, Cell Cycle 13(2) 173-174.
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.
Heim, A., Rothhaemel, S., Hartung, O., Jenny, A., Marlow, F.L. (2014). Oocyte polarity requires regulation of bucky ball via its 3'UTR. Development 141(4), 842-54.
Serysheva, E., Berhane, H., Grumolato, L., Demir, K., Balmer, S., Bodak, M. , Aaronson, S., Boutros, M., Mlodzik*, M., Jenny, A*. (2013). Wnk kinases are positive regulators of canonical Wnt/b-catenin signaling. EMBO Reports doi: 10.1038/embor.2013.88
Müller, R., Jenny, A.*, Stanley, P*. (2013) The extracellular GlcNac transferase Eogt interact with the Notch signaling and pyrimidine metabolism. PLoS ONE 8: e62835. doi:10.1371
Santos-Ledo, A., Jenny, A.*, Marlow, F*.(2012) Comparative gene expression analysis of the fmnl family of formins during zebrafish development and implications for tissue-specific functions. Gene Expr. Patterns. pii: S1567-133X(12)00076-2.
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. 18, 665-72.
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 503
Bronx, NY 10461