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/Fx-planar cellular polarity (PCP) pathway, resulting the polarization of cells within the pane of the epithelium. These two pathways are highly conserved between humans, mice, fish, and flies. Canonical Wnt/β-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 the kidney, where their lack causes hypertension (Gordon syndrome).
Non-canonical Wnt signaling established polarity within the plane o an epithelium, commonly referred to as epithelial planar cell polarity (PCP) and allows a cell to form structures that require not only positional, but also vectorial information. 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. 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 GENETIC MODEL FOR ENDOSOMAL MICROAUTOPHAGY
Autophagy delivers cytosolic components to lysosomes for degradation and is thus essential for cellular homeostasis and to cope with different stressors. As such, autophagy counteracts various human diseases and its reduction leads to aging like phenotypes. Macroautophagy (MA) can selectively degrade organelles or aggregated proteins, but selective degradation of single proteins has only been described for Chaperone-mediated autophagy (CMA) and endosomal Microautophagy (eMI). These two autophagic pathways, described to date only in mammals, are specific for proteins containing KFERQ-related targeting motifs. In collaboration with the Cuervo lab, we have developed a fluorescent reporter to characterize an eMI or CMA-like process in Drosophila in vivo. Our data provide evidence for a novel, starvation inducible catabolic process resembling endosomal microautophagy in a non-mammalian species. We are thus for the first time able to perform genetic screens for regulatory components of eMI, this only recently identified form of autophagy about which barely anything is known.
It is our goal to use Drosophila as model system to address fundamental questions that are relevant for development and disease in general.
Reviews and commentaries
Baker, N.E. **, Jenny, A.** (2014) Metabolism and the other fat: a protocadherin in mitochondria (Preview). Cell 158, 1240-1. PMID: 25215484.
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.
Primary Articles (selection)
Jahanshahi, M., Hsiao, K., Jenny, A., Pfleger, C. M. (2016) The Hippo Pathway targets the Cdh1/fzr inhibitor Rae1 to regulate mitosis and establish organ size. PLoS Genetics in press.
Mukherjee, A., Patel, B., Koga, H., Cuervo, AM., Jenny, A. (2016). Selective endosomal microautophagy is starvation inducible in Drosophila. Autophagy in press.
Dollar, G., Barnett, A.A., Gombos, R., Sanchez Hernandez, D., Maung, S.M.T, Mihály, Jenny, A. (2016). Unique and overlapping functions of formins Frl and DAAM during PCP signaling and neuronal development in Drosophila. Genetics 202 (3), 1135-1151.
Gombos, R., Migh, E., Antal, O., Mukherjee, A., Jenny, A., Mihály, J. (2015)The Formin DAAM Functions as Molecular Effector of the Planar Cell Polarity Pathway during Axonal Development in Drosophila. J. Neuroscience, 35 (28),10154-67.
Fagan, J.K., Dollar, G., Lu, Q., Barnett, A., Pechuan Jorge, J., Schlosser, A., Pfleger, C., Adler, P., Jenny, A..* (2014) Combover/ CG10732, a novel PCP effector for Drosophila wing hair formation. PLoS One,9(9):e107311. doi: 10.1371. PMID: 25207969.
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.
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.*, 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.
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.
*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