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PMID: 23040479 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The Par complex and integrins direct asymmetric cell division in adult intestinal stem cells.

Cell stem cell ·Vol. 11 ·No. 4 ·2012-10-05 ·Pages 529-40

Goulas S, Conder R, Knoblich JA

Abstract

The adult Drosophila midgut is maintained by intestinal stem cells (ISCs) that generate both self-renewing and differentiating daughter cells. How this asymmetry is generated is currently unclear. Here, we demonstrate that asymmetric ISC division is established by a unique combination of extracellular and intracellular polarity mechanisms. We show that Integrin-dependent adhesion to the basement membrane induces cell-intrinsic polarity and results in the asymmetric segregation of the Par proteins Par-3, Par-6, and aPKC into the apical daughter cell. Cell-specific knockdown and overexpression experiments suggest that increased activity of aPKC enhances Delta/Notch signaling in one of the two daughter cells to induce terminal differentiation. Perturbing this mechanism or altering the orientation of ISC division results in the formation of intestinal tumors. Our data indicate that mechanisms for intrinsically asymmetric cell division can be adapted to allow for the flexibility in lineage decisions that is required in adult stem cells.

MeSH Terms
Adult Stem Cells/physiology Animals Asymmetric Cell Division Cell Differentiation Cell Polarity Cell Proliferation Cell Survival Cells, Cultured Drosophila Proteins/genetics,metabolism Drosophila melanogaster/cytology,physiology Integrins/metabolism Intestines/cytology Intracellular Signaling Peptides and Proteins/genetics,metabolism Multiprotein Complexes/metabolism Protein Kinase C/genetics,metabolism Protein Transport Receptors, Notch/metabolism
Chemicals
Drosophila Proteins Integrins Intracellular Signaling Peptides and Proteins Multiprotein Complexes N protein, Drosophila Receptors, Notch baz protein, Drosophila PKC-3 protein Par-6 protein, Drosophila Protein Kinase C
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Goulas Spyros
Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
Conder Ryan
Knoblich Juergen A
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Article Info
Journal
Cell stem cell
Abbr.
Cell Stem Cell
ISSN
1875-9777
DOI
10.1016/j.stem.2012.06.017
Published
2012-10-05
Pages
529-40
Language
English
Region
United States
NLM ID
101311472
PMCID
PMC3465556
Subset
IM
Grants
European Research Council · 250342 · International
External Links
PubMed source DOI: 10.1016/j.stem.2012.06.017 PMC Full Text View journal details
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