Planar cell polarity and the cytoskeleton Planar cell polarity (PCP) signaling regulates the establishment of polarity within the plane of an epithelium. The results of signaling are as diverse as the determination of cell fates, the generation of asymmetric, but highly aligned structures (e.g. stereocilia in the human inner ear or hairs on a fly wing), or the directional migration of cells during convergent extension during vertebrate gastrulation. PCP is governed by the non-canonical Fz/Planar Cell Polarity pathway, in which a Wnt signals through a Frizzled receptor leading to nuclear responses, as well as to cytoskeletal changes mediated by Rho Kinase. PCP signaling was originally discovered and is best studied in Drosophila, mainly because of the versatility of the fly as model system due to its low genetic redundancy. In Drosophila, PCP is essential for the orientation of the actin wing hairs and the polarization of the ommatidia in the eye, requiring highly coordinated movement of groups of photoreceptor cells (ommatidial rotation). Thus, key to PCP signaling in flies, and to convergent extension in vertebrates, are cytoskeletal rearrangements and cell migration processes. Central to these processes is Rho Kinase (Rock, Drok in Drosophila), mutations in which or dominant negative forms of which lead to ommatidial rotation/migration and convergent extension/neural tube defects in flies and fish, respectively. This proposal focuses on biochemical and genetic approaches to identify and characterize new PCP components and regulators of the cytoskeleton. In a genome wide screen we identified direct Drok substrates using a phosphorylation induced gel-shift assay. We will characterize the candidates using in vivo RNAi, mutational analysis and genetic interaction assays with known pathway components. We propose to study their mechanism of action with respect to Rho Kinase and PCP signaling in detail. Using the above strategies to work out mechanistic aspects of PCP signaling as well as to discover new links to cellular responses will extend our knowledge of early development. Due to the conservation of the PCP gene network in organisms as diverse as flies, ascidians and mammals, the proposed research will be of immediate importance for the understanding of the establishment of PCP and related morphogenetic processes in vertebrates.

Public Health Relevance

The mechanism of communication between cells of the fruitfly Drosophila and humans is well conserved and very similar. We make use of Drosophila to study how cell communication affects cell movement. Lack of such communication can lead to severe birth defects such as open neural tubes (e.g. spina bifida).

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Development - 1 Study Section (DEV1)
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Hoodbhoy, Tanya
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Albert Einstein College of Medicine
Anatomy/Cell Biology
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Dollar, Gretchen; Gombos, Rita; Barnett, Austen A et al. (2016) Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila. Genetics 202:1135-51
Gombos, Rita; Migh, Ede; Antal, Otilia et al. (2015) The Formin DAAM Functions as Molecular Effector of the Planar Cell Polarity Pathway during Axonal Development in Drosophila. J Neurosci 35:10154-67
Forbes, Meredyth M; Rothhämel, Sophie; Jenny, Andreas et al. (2015) Maternal dazap2 Regulates Germ Granules by Counteracting Dynein in Zebrafish Primordial Germ Cells. Cell Rep 12:49-57
Serysheva, Ekatherina; Mlodzik, Marek; Jenny, Andreas (2014) WNKs in Wnt/β-catenin signaling. Cell Cycle 13:173-4
Baker, Nicholas E; Jenny, Andreas (2014) Metabolism and the other fat: a protocadherin in mitochondria. Cell 158:1240-1
Heim, Amanda E; Hartung, Odelya; Rothhämel, Sophie et al. (2014) Oocyte polarity requires a Bucky ball-dependent feedback amplification loop. Development 141:842-54
Fagan, Jeremy K; Dollar, Gretchen; Lu, Qiuheng et al. (2014) Combover/CG10732, a novel PCP effector for Drosophila wing hair formation. PLoS One 9:e107311
Santos-Ledo, Adrián; Jenny, Andreas; Marlow, Florence L (2013) Comparative gene expression analysis of the fmnl family of formins during zebrafish development and implications for tissue specific functions. Gene Expr Patterns 13:30-7
Müller, Reto; Jenny, Andreas; Stanley, Pamela (2013) The EGF repeat-specific O-GlcNAc-transferase Eogt interacts with notch signaling and pyrimidine metabolism pathways in Drosophila. PLoS One 8:e62835
Serysheva, Ekatherina; Berhane, Hebist; Grumolato, Luca et al. (2013) Wnk kinases are positive regulators of canonical Wnt/β-catenin signalling. EMBO Rep 14:718-25

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