Document Detail

Cortical aPKC kinase activity distinguishes neural stem cells from progenitor cells by ensuring asymmetric segregation of Numb.
MedLine Citation:
PMID:  22394487     Owner:  NLM     Status:  MEDLINE    
During asymmetric stem cell division, polarization of the cell cortex targets fate determinants unequally into the sibling daughters, leading to regeneration of a stem cell and production of a progenitor cell with restricted developmental potential. In mitotic neural stem cells (neuroblasts) in fly larval brains, the antagonistic interaction between the polarity proteins Lethal (2) giant larvae (Lgl) and atypical Protein Kinase C (aPKC) ensures self-renewal of a daughter neuroblast and generation of a progenitor cell by regulating asymmetric segregation of fate determinants. In the absence of lgl function, elevated cortical aPKC kinase activity perturbs unequal partitioning of the fate determinants including Numb and induces supernumerary neuroblasts in larval brains. However, whether increased aPKC function triggers formation of excess neuroblasts by inactivating Numb remains controversial. To investigate how increased cortical aPKC function induces formation of excess neuroblasts, we analyzed the fate of cells in neuroblast lineage clones in lgl mutant brains. Surprisingly, our analyses revealed that neuroblasts in lgl mutant brains undergo asymmetric division to produce progenitor cells, which then revert back into neuroblasts. In lgl mutant brains, Numb remained localized in the cortex of mitotic neuroblasts and failed to segregate exclusively into the progenitor cell following completion of asymmetric division. These results led us to propose that elevated aPKC function in the cortex of mitotic neuroblasts reduces the function of Numb in the future progenitor cells. We identified that the acyl-CoA binding domain containing 3 protein (ACBD3) binding region is essential for asymmetric segregation of Numb in mitotic neuroblasts and suppression of the supernumerary neuroblast phenotype induced by increased aPKC function. The ACBD3 binding region of Numb harbors two aPKC phosphorylation sites, serines 48 and 52. Surprisingly, while the phosphorylation status at these two sites directly impinged on asymmetric segregation of Numb in mitotic neuroblasts, both the phosphomimetic and non-phosphorylatable forms of Numb suppressed formation of excess neuroblasts triggered by increased cortical aPKC function. Thus, we propose that precise regulation of cortical aPKC kinase activity distinguishes the sibling cell identity in part by ensuring asymmetric partitioning of Numb into the future progenitor cell where Numb maintains restricted potential independently of regulation by aPKC.
Jill M Haenfler; Chaoyuan Kuang; Cheng-Yu Lee
Related Documents :
77187 - Epidermla cell kinetics in hairless mice after bleomycin. i. perturbations after differ...
7519747 - Antiproliferative effect of tumor necrosis factor-alpha on human glioblastoma cells lin...
20333647 - Role of voltage-gated potassium channels in the fate determination of embryonic stem ce...
9728657 - Paclitaxel-induced modification of the effects of radiation and alterations in the cell...
24509857 - A critical role for the neural zinc factor st18 in pancreatic beta-cell apoptosis.
19375227 - Investigation of photoconductivity of silicon solar cells by a near-field scanning micr...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-25
Journal Detail:
Title:  Developmental biology     Volume:  365     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-09     Completed Date:  2013-06-25     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  219-28     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Brain / embryology
Cell Differentiation
Cell Lineage
Drosophila Proteins / metabolism*
Drosophila melanogaster / cytology*,  embryology,  enzymology
Enzyme Activation
Juvenile Hormones / metabolism*
Neural Stem Cells / enzymology*
Neurons / cytology,  enzymology
Protein Kinase C-alpha / metabolism*
Stem Cells / enzymology*
Grant Support
Reg. No./Substance:
0/Drosophila Proteins; 0/Juvenile Hormones; 0/numb protein, Drosophila; EC Kinase C-alpha

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Nemo phosphorylates Eyes absent and enhances output from the Eya-Sine oculis transcriptional complex...
Next Document:  Diagnostic value of anti-mutated citrullinated vimentin in comparison to anti-cyclic citrullinated p...