Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia

Abstract

Cell polarity is essential for generating cell diversity and for the proper function of most differentiated cell types. In many organisms, cell polarity is regulated by the atypical protein kinase C (aPKC), Bazooka (Baz/Par3), and Par6 proteins. Here, we show that Drosophila aPKC zygotic null mutants survive to mid-larval stages, where they exhibit defects in neuroblast and epithelial cell polarity. Mutant neuroblasts lack apical localization of Par6 and Lgl, and fail to exclude Miranda from the apical cortex; yet, they show normal apical crescents of Baz/Par3, Pins, Inscuteable, and Discs large and normal spindle orientation. Mutant imaginal disc epithelia have defects in apical/basal cell polarity and tissue morphology. In addition, we show that aPKC mutants show reduced cell proliferation in both neuroblasts and epithelia, the opposite of the lethal giant larvae (lgl) tumor suppressor phenotype, and that reduced aPKC levels strongly suppress most lgl cell polarity and overproliferation phenotypes.

Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors

“…These defects are quite reminiscent of those seen in lgl mutant brains (Rolls et al 2003). Among the many proteins mislocalized in Lgl1 mutant neuroepithelial cells is Numb, whose asymmetric inheritance in dividing cells influences a Notch signal-dependent pathway through which neural progenitors become differentiated neurons.…”

“…In zygotic mutant larvae, neuroblasts and ganglion mother cells overproliferate, giving rise to characteristically elongated optic lobes (Gateff and Schneiderman 1969;Woods and Bryant 1989). The comparative dynamics of proliferation in wild-type and mutant neural tissue are only now being closely studied (Rolls et al 2003). However, normal larval neuroblasts are proliferative, polarized, and express nTSG proteins, thus it is reasonable to assume that they may be affected in a manner similar to the neoplastic epithelium.…”

Oncostatin M-stimulated Apical Plasma Membrane Biogenesis Requires p27Kip1-Regulated Cell Cycle Dynamics

“…Impairment of these events may cause a loss of apical-basolateral asymmetry and may lead to deranged cell growth (Bilder et al, 2000;Vermeer et al, 2003;Baas et al, 2004) or spindle misorientation . Recent studies have reported an evolutionary conserved genetic program that may link the process of polarity development and proliferation (Bilder et al, 2000;Humbert et al, 2003;Rolls et al, 2003;Klezovitch et al, 2004). However, many aspects of such a link remain unclear, e.g., the extent to which cell proliferation can directly affect epithelial cell organization or vice versa.…”

aPKCζ cortical loading is associated with Lgl cytoplasmic release and tumor growth in Drosophila and human epithelia

“…A genetic link between cell shape and proliferation is given by molecules involved in the establishment and maintenance of apical-basal cell polarity in the epithelial tissues. The atypical protein kinase C (aPKC) proteins are a subgroup of the PKC family of serine-threonine protein kinases that comprise the i/l and z isoforms in mammals, whereas only the aPKCz isoform exists in Drosophila (Suzuki et al, 2001;Rolls et al, 2003;Kovac et al, 2007). These proteins belong to the evolutionarily conserved PAR apical complex (Harris and Peifer, 2004;Suzuki and Ohno, 2006) and are involved in the determination of the apical identity both in the invertebrate and vertebrate epithelial cells.…”