Par3–mInsc and Gαi3 cooperate to promote oriented epidermal cell divisions through LGN
| Autor: | Maria Pia Postiglione, Juergen A. Knoblich, Scott E. Williams, Elaine Fuchs, Lyndsay A. Ratliff |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Mice 129 Strain genetic structures Morphogenesis Cell Cycle Proteins Mice Transgenic Spindle Apparatus GTP-Binding Protein alpha Subunits Gi-Go Biology Models Biological Article Mice Pregnancy RNA interference GNAI3 Animals Progenitor cell Adaptor Proteins Signal Transducing Body Patterning Regulation of gene expression Epidermis (botany) Gene Expression Regulation Developmental Signal transducing adaptor protein Cell Differentiation Cell Biology Cell biology Mice Inbred C57BL Epidermal Cells Gene Knockdown Techniques Female RNA Interference Epidermis GTP-Binding Protein alpha Subunit Gi2 Stem cell Carrier Proteins Cell Adhesion Molecules Cell Division |
| Zdroj: | Nature Cell Biology. 16:758-769 |
| ISSN: | 1476-4679 1465-7392 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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