Marek Mlodzik’s laboratory studies the establishment of epithelial planar cell polarity (PCP) regulated by Wnt/Frizzled-PCP signaling and the mechanisms of Wnt-signaling specificity regulation between the PCP and canonical beta-catenin pathways. In addition, we are interested in cross-talk between the Wnt/Frizzled pathways and Notch and Egf-receptor signaling.
Epithelial cells - in the epidermis as well as in neural epithelia - are polarized with respect to the body axis. This is not only the case in Drosophila and other insects but is a widespread feature of epithelia in both invertebrates and vertebrates. The apparent difference between whole epithelial tissue (such as the disc-epithelia in Drosophila) and cells in tissue culture is that, in addition to the apical-basolateral polarity, epithelial tissues develop an obvious polarity with respect to body axes, planar cell polarity or PCP. The Drosophila tissue polarity genes are required for correct PCP generation and mutations in them affect all epithelial tissues (both neuronal and non-neuronal). Efforts to understand the mechanisms of PCP formation have focused on the wing and the eye. In the wing, PCP is reflected in the choice of the site at which hair out-growth initiates in each cell and the direction the hair points. In the eye, PCP is reflected in the mirror-symmetric arrangement of ommatidia relative to the dorso-ventral midline, the equator. PCP mutations result in the loss of hair/bristle polarity in the wing and loss of mirror-image symmetry in the eye, with ommatidia being misrotated and adopting the chiral forms randomly. Recent findings indicate that the underlying signaling pathway(s) are not only conserved throughout evolution and regulate related aspects of coordinated cellular polarization in mammals, but that they are also linked to several human diseases, ranging from gastrulation defects to cancer, and from ciliopathies (including obesity and mental retardation) to deafness and sterility.
For more information, please visit the http://labs.icahn.mssm.edu/mlodziklab/ website.
