Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation.
How a cell chooses to proliferate or to differentiate is an important issue in stem cell and cancer biology. Drosophila neuroblasts undergo self-renewal with every cell division, producing another neuroblast and a differentiating daughter cell, but the mechanisms controlling the self-renewal/differentiation decision are poorly understood. Here we tested whether cell polarity genes, known to regulate embryonic neuroblast asymmetric cell division, also regulate neuroblast self-renewal. Clonal analysis in larval brains showed that pins mutant neuroblasts rapidly fail to self-renew, whereas lethal giant larvae (lgl) mutant neuroblasts generate multiple neuroblasts. Notably, lgl pins double mutant neuroblasts all divide symmetrically to self-renew, filling the brain with neuroblasts at the expense of neurons. The lgl pins neuroblasts show ectopic cortical localization of atypical protein kinase C (aPKC), and a decrease in aPKC expression reduces neuroblast numbers, suggesting that aPKC promotes neuroblast self-renewal. In support of this hypothesis, neuroblast-specific overexpression of membrane-targeted aPKC, but not a kinase-dead version, induces ectopic neuroblast self-renewal. We conclude that cortical aPKC kinase activity is a potent inducer of neuroblast self-renewal.
Lee
Cheng-Yu
CY
Institutes of Neuroscience and Molecular Biology, Howard Hughes Medical Institute, University of Oregon 1254, Eugene, Oregon 97403, USA.
Robinson
Kristin J
KJ
Doe
Chris Q
CQ
D000818:Animals; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002455:Cell Division; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; C405164:Pins protein, Drosophila; D025521:Tumor Suppressor Proteins; C081435:l(2)gl protein, Drosophila; C115015:PKC-3 protein; D011493:Protein Kinase C