Par3-mInsc and Gα i3 cooperate to promote oriented epidermal cell divisions through LGN Journal Article

Author(s): Williams, Scott E; Ratliff, Lyndsay A; Postiglione, Maria P; Knoblich, Juergen A; Fuchs, Elaine V
Article Title: Par3-mInsc and Gα i3 cooperate to promote oriented epidermal cell divisions through LGN
Affiliation IST Austria
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 Gα i3. 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 Gα i3 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.
Keywords: unclassified drug; G alpha i3 protein; heterotrimeric guanine nucleotide binding protein; LGN protein; mlnsc protein; par3 protein
Journal Title: Nature Cell Biology
Volume: 16
Issue 8
ISSN: 1476-4679
Publisher: Nature Publishing Group  
Date Published: 2014-08-01
Start Page: 758
End Page: 769
Sponsor: S.E.W. was supported by an American Cancer Society postdoctoral fellowship and E.F. is an investigator in the Howard Hughes Medical Institute. Work in the Fuchs laboratory was supported by a grant from the National Institutes of Health (E.F. R37-27883)
DOI: 10.1038/ncb3001
Open access: no