title: Par3-mInsc and Gαi3 cooperate to promote oriented epidermal cell divisions through LGN.
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.
authors.affiliation: 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.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Williams
authors.affiliation: Department of Pathology &Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Lyndsay A
authors.initials: LA
authors.lastname: Ratliff
authors.affiliation: 1] Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria [2].
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Postiglione
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria.
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Knoblich
authors.affiliation: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology &Development, The Rockefeller University, 1230 York Avenue, Box 300, New York, New York 10065, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019521:Body Patterning; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology / Q000502:physiology*; D005260:Female; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D011247:Pregnancy; D034622:RNA Interference; D008941:Spindle Apparatus / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; C502655:LGN protein, mouse; C115084:Pard3 protein, mouse; C561632:inscuteable protein, mouse; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498016:Gnai2 protein, mouse; C417708:Gnai3 protein, mouse