Polarization of Drosophila neuroblasts during asymmetric division.
During Drosophila development, neuroblasts divide to generate progeny with two different fates. One daughter cell self-renews to maintain the neuroblast pool, whereas the other differentiates to populate the central nervous system. The difference in fate arises from the asymmetric distribution of proteins that specify either self-renewal or differentiation, which is brought about by their polarization into separate apical and basal cortical domains during mitosis. Neuroblast symmetry breaking is regulated by numerous proteins, many of which have only recently been discovered. The atypical protein kinase C (aPKC) is a broad regulator of polarity that localizes to the neuroblast apical cortical region and directs the polarization of the basal domain. Recent work suggests that polarity can be explained in large part by the mechanisms that restrict aPKC activity to the apical domain and those that couple asymmetric aPKC activity to the polarization of downstream factors. Polarized aPKC activity is created by a network of regulatory molecules, including Bazooka/Par-3, Cdc42, and the tumor suppressor Lgl, which represses basal recruitment. Direct phosphorylation by aPKC leads to cortical release of basal domain factors, preventing them from occupying the apical domain. In this framework, neuroblast polarity arises from a complex system that orchestrates robust aPKC polarity, which in turn polarizes substrates by coupling phosphorylation to cortical release.
Prehoda
Kenneth E
KE
Department of Chemistry and Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, USA. prehoda@molbio.uoregon.edu
D000818:Animals; D019521:Body Patterning; D002454:Cell Differentiation; D002455:Cell Division; D004330:Drosophila / Q000378:metabolism*; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism; D008941:Spindle Apparatus; D013234:Stem Cells / Q000166:cytology
D020033:Protein Isoforms; D011493:Protein Kinase C