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Nat Cell Biol. 2014 Aug;16(8):758-69. doi: 10.1038/ncb3001. Epub 2014 Jul 13.

Par3-mInsc and Gαi3 cooperate to promote oriented epidermal cell divisions through LGN.

Author information

1
1] Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology &Development, The Rockefeller University, 1230 York Avenue, Box 300, New York, New York 10065, USA [2] Department of Pathology &Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
2
Department of Pathology &Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
3
1] Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria [2].
4
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria.
5
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology &Development, The Rockefeller University, 1230 York Avenue, Box 300, New York, New York 10065, USA.

Abstract

Asymmetric cell divisions allow stem cells to balance proliferation and differentiation. During embryogenesis, murine epidermis expands rapidly from a single layer of unspecified basal layer progenitors to a stratified, differentiated epithelium. Morphogenesis involves perpendicular (asymmetric) divisions and the spindle orientation protein LGN, but little is known about how the apical localization of LGN is regulated. Here, we combine conventional genetics and lentiviral-mediated in vivo RNAi to explore the functions of the LGN-interacting proteins Par3, mInsc and Gαi3. Whereas loss of each gene alone leads to randomized division angles, combined loss of Gnai3 and mInsc causes a phenotype of mostly planar divisions, akin to loss of LGN. These findings lend experimental support for the hitherto untested model that Par3-mInsc and Gαi3 act cooperatively to polarize LGN and promote perpendicular divisions. Finally, we uncover a developmental switch between delamination-driven early stratification and spindle-orientation-dependent differentiation that occurs around E15, revealing a two-step mechanism underlying epidermal maturation.

PMID:
25016959
PMCID:
PMC4159251
DOI:
10.1038/ncb3001
[Indexed for MEDLINE]
Free PMC Article

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