Diego localizes to the distal edge of pupal wing cells
The Jenny Lab

Department of
Developmental and Molecular Biology at

Albert Einstein

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Science at the Heart of Medicine
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Epithelial cells are polarized in multiple ways. Apical-basolateral polarity (perpendicular to the plane of the epithelial sheath) enables a cell to directionally transport molecules across a cell layer (e.g. in the gut, kidney and glands) and selectively secrete extracellular matrix components to form a basal lamina. To perform many of their functions, epithelia frequently also are polarized within the plane of the epithelium. The latter polarization is 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 and cell fate specifications. Examples of PCP in vertebrates can be very obvious, as in the ordered arrangement of scales on fish, feathers of birds, and hairs of mammalian skin. Less visible examples are the cilia of the lung and oviduct as well as the stereocilia of the sensory epithelium of the organ of Corti in the vertebrate inner ear. Aberrant PCP of the sensory epithelium in the organ of Corti leads to deafness. Furthermore, the complicated movement of mesenchymal cells during gastrulation (called convergent&extension) that leads to the elongation and thinning of the body axis also depends on correct PCP signaling. Failure PCP signaling can lead to left-right asymmetry defects, limb defects, ciliary diseases, and neural tube defects such as spina bifida.

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 on several external adult structures such as the bristles on the thorax or the precisely aligned hairs on wing cells. In addition, the facet eye also shows characteristics of PCP with its precise arrangement of each building block, the ommatidium, with respect to each other and the general axes in each eye. 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. We have performed a genome wide substrate screen for novel Rho kinase substrates and are currently using genetic and molecular approaches to address their function in the PCP signaling pathway. In collaboration with the Marlow lab at Einstein, we also look at the function of the zebrafish homologs of some of our newly identified substrates.

PCP phenotype of a novel Rho kinase target:

RNAi mwh

In vivo knock-down of a novel Rho kinase substrate leads to PCP signaling defects in the eye.

 

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