Transcriptional Control of Apical-Basal Polarity Regulators

Abstract

Cell polarity is essential for many functions of cells and tissues including the initial establishment and subsequent maintenance of epithelial tissues, asymmetric cell division, and morphogenetic movements. Cell polarity along the apical-basal axis is controlled by three protein complexes that interact with and co-regulate each other: The Par-, Crumbs-, and Scrib-complexes. The localization and activity of the components of these complexes is predominantly controlled by protein-protein interactions and protein phosphorylation status. Increasing evidence accumulates that, besides the regulation at the protein level, the precise expression control of polarity determinants contributes substantially to cell polarity regulation. Here we review how gene expression regulation influences processes that depend on the induction, maintenance, or abolishment of cell polarity with a special focus on epithelial to mesenchymal transition and asymmetric stem cell division. We conclude that gene expression control is an important and often neglected mechanism in the control of cell polarity.

Keywords: Crumbs complex; Par complex; Scrib complex; asymmetric cell division; cell polarity; epithelial to mesenchymal transition; gene expression; transcriptional regulation.

Figure 1

Overview of cell polarity determinants in Drosophila epithelia and neuroblasts. (A) Epithelial cells are polarized along the apicobasal axis. The Crb and Par complexes localize apically, and components of these complexes can interact with each other. In Drosophila, this region is referred to as the subapical region (SAR). In addition, Baz/Par-3 interacts with adherens junctions (AJ). The Par complex kinase aPKC phosphorylates Lgl, restricting the Scrib complex to the basolateral side of the cell, where it localizes cortically with the other members of the Scrib complex: Scrib and Dlg. At the basolateral side of the cell Lgl inhibits aPKC. (B) The Drosophila neuroblast (NB) is widely used as a model to study asymmetric stem cell division. Mitotic neuroblasts display apicobasal polarity. Components of the Par and Scrib complexes are apically localized. Further, Insc and its interactor Pins localize apically and orient the spindle apparatus. Neuroblast division results in two distinct daughter cells: the apical cell inherits apical determinants and maintains neuroblast fate. The basally formed cell, called ganglion mother cell (GMC), inherits basally localized differentiation factors and divides to produce neurons.