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

Rolls, Melissa M.; Albertson, Roger; Shih, Hsin-Pei; Lee, Cheng-Yu; Doe, Chris Q.

doi:10.1083/jcb.200306079

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

Journal Article · 01 December 2003 · Journal of Cell Biology

DOI: https://doi.org/10.1083/jcb.200306079 · OSTI ID:1625129

Rolls, Melissa M. ^[1]; Albertson, Roger ^[1]; Shih, Hsin-Pei ^[1]; Lee, Cheng-Yu ^[1]; Doe, Chris Q. ^[1]

Univ. of Oregon, Eugene, OR (United States). Howard Hughes Medical Institute, Institutes of Neuroscience and Molecular Biology

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 demonstrate 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.

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Research Organization:: Univ. of Oregon, Eugene, OR (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institutes of Health (NIH); Howard Hughes Medical Institute

OSTI ID:: 1625129

Journal Information:: Journal of Cell Biology, Vol. 163, Issue 5; ISSN 0021-9525

Publisher:: Rockefeller University PressCopyright Statement

Country of Publication:: United States

Language:: English

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DaPKC-dependent phosphorylation of Crumbs is required for epithelial cell polarity in Drosophila Sotillos, Sol; Díaz-Meco, María Teresa; Caminero, Eva The Journal of Cell Biology, Vol. 166, Issue 4 https://doi.org/10.1083/jcb.200311031	journal	August 2004
The positioning and segregation of apical cues during epithelial polarity establishment in Drosophila Harris, Tony J. C.; Peifer, Mark Journal of Cell Biology, Vol. 170, Issue 5 https://doi.org/10.1083/jcb.200505127	journal	August 2005
Control of T helper cell differentiation through cytokine receptor inclusion in the immunological synapse Maldonado, Roberto A.; Soriano, Michelle A.; Perdomo, L. Carolina Journal of Experimental Medicine, Vol. 206, Issue 4 https://doi.org/10.1084/jem.20082900	journal	April 2009
Asymmetric cortical extension shifts cleavage furrow position inDrosophilaneuroblasts Connell, Marisa; Cabernard, Clemens; Ricketson, Derek Molecular Biology of the Cell, Vol. 22, Issue 22 https://doi.org/10.1091/mbc.e11-02-0173	journal	November 2011
Apical–basal polarity in Drosophila neuroblasts is independent of vesicular trafficking Halbsgut, Nils; Linnemannstöns, Karen; Zimmermann, Laura Isabel Molecular Biology of the Cell, Vol. 22, Issue 22 https://doi.org/10.1091/mbc.e11-03-0219	journal	November 2011
Epithelial polarity and spindle orientation: intersecting pathways Bergstralh, Dan T.; Haack, Timm; St Johnston, Daniel Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 368, Issue 1629 https://doi.org/10.1098/rstb.2013.0291	journal	November 2013
aPKC-mediated displacement and actomyosin-mediated retention polarize Miranda in Drosophila neuroblasts Hannaford, Matthew; Ramat, Anne; Loyer, Nicolas https://doi.org/10.1101/148213	posted_content	June 2017
Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo pathway signaling Doggett, Karen; Grusche, Felix A.; Richardson, Helena E. BMC Developmental Biology, Vol. 11, Issue 1 https://doi.org/10.1186/1471-213x-11-57	journal	January 2011
A modifier screen in the Drosophila eye reveals that aPKC interacts with Glued during central synapse formation Ma, Lisha; Johns, Louise A.; Allen, Marcus J. BMC Genetics, Vol. 10, Issue 1 https://doi.org/10.1186/1471-2156-10-77	journal	November 2009
A mosaic genetic screen for novel mutations affecting Drosophila neuroblast divisions Slack, Cathy; Somers, W. Gregory; Sousa-Nunes, Rita BMC Genetics, Vol. 7, Issue 1 https://doi.org/10.1186/1471-2156-7-33	journal	June 2006
Bazooka mediates secondary axon morphology in Drosophila brain lineages Spindler, Shana R.; Hartenstein, Volker Neural Development, Vol. 6, Issue 1 https://doi.org/10.1186/1749-8104-6-16	journal	January 2011
Uncovering the link between malfunctions in Drosophila neuroblast asymmetric cell division and tumorigenesis Kelsom, Corey; Lu, Wange Cell & Bioscience, Vol. 2, Issue 1 https://doi.org/10.1186/2045-3701-2-38	journal	January 2012
Spermatid Cyst Polarization in Drosophila Depends upon apkc and the CPEB Family Translational Regulator orb2 Xu, Shuwa; Tyagi, Sanjay; Schedl, Paul PLoS Genetics, Vol. 10, Issue 5 https://doi.org/10.1371/journal.pgen.1004380	journal	May 2014
Functional Interactions between the erupted/tsg101 Growth Suppressor Gene and the DaPKC and rbf1 Genes in Drosophila Imaginal Disc Tumors Gilbert, M. Melissa; Robinson, Brian S.; Moberg, Kenneth H. PLoS ONE, Vol. 4, Issue 9 https://doi.org/10.1371/journal.pone.0007039	journal	September 2009
Role of Kinesin Heavy Chain in Crumbs Localization along the Rhabdomere Elongation in Drosophila Photoreceptor League, Garrett P.; Nam, Sang-Chul PLoS ONE, Vol. 6, Issue 6 https://doi.org/10.1371/journal.pone.0021218	journal	June 2011
Pins is not required for spindle orientation in the Drosophila wing disc. Bergstralh, Dan T.; Lovegrove, Holly E.; Kujawiak, Izabela The Company of Biologists https://doi.org/10.17863/cam.485	journalarticle	January 2016
A Glutamine-Rich Factor Affects Stem Cell Genesis in Leech Hohenstein, Kristi A.; Lang, Shirley A.; Nuthulaganti, Tej Stem Cells International, Vol. 2010 https://doi.org/10.4061/2010/145183	journal	January 2010
Vibrator and PI4KIIIα govern neuroblast polarity by anchoring non-muscle myosin II Koe, Chwee Tat; Tan, Ye Sing; Lönnfors, Max eLife, Vol. 7 https://doi.org/10.7554/elife.33555	journal	February 2018
Asymmetric recruitment and actin-dependent cortical flows drive the neuroblast polarity cycle Oon, Chet Huan; Prehoda, Kenneth E. eLife, Vol. 8 https://doi.org/10.7554/elife.45815	journal	May 2019
Stepwise polarisation of developing bilayered epidermis is mediated by aPKC and E-cadherin in zebrafish Arora, Prateek; Dongre, Shivali; Raman, Renuka eLife, Vol. 9 https://doi.org/10.7554/elife.49064	journal	January 2020

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

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