Programmed Cell-to-Cell Variability in Ras Activity Triggers Emergent Behaviors during Mammary Epithelial Morphogenesis
Variability in signaling pathway activation between neighboring epithelial cells can arise from local differences in the microenvironment, noisy gene expression, or acquired genetic changes. To investigate the consequences of this cell-to-cell variability in signaling pathway activation on coordinat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712002781 |
| _version_ | 1828453301346107392 |
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| author | Jennifer S. Liu Justin T. Farlow Amanda K. Paulson Mark A. Labarge Zev J. Gartner |
| author_facet | Jennifer S. Liu Justin T. Farlow Amanda K. Paulson Mark A. Labarge Zev J. Gartner |
| author_sort | Jennifer S. Liu |
| collection | DOAJ |
| description | Variability in signaling pathway activation between neighboring epithelial cells can arise from local differences in the microenvironment, noisy gene expression, or acquired genetic changes. To investigate the consequences of this cell-to-cell variability in signaling pathway activation on coordinated multicellular processes such as morphogenesis, we use DNA-programmed assembly to construct three-dimensional MCF10A microtissues that are mosaic for low-level expression of activated H-Ras. We find two emergent behaviors in mosaic microtissues: cells with activated H-Ras are basally extruded or lead motile multicellular protrusions that direct the collective motility of their wild-type neighbors. Remarkably, these behaviors are not observed in homogeneous microtissues in which all cells express the activated Ras protein, indicating that heterogeneity in Ras activity, rather than the total amount of Ras activity, is critical for these processes. Our results directly demonstrate that cell-to-cell variability in pathway activation within local populations of epithelial cells can drive emergent behaviors during epithelial morphogenesis. |
| first_indexed | 2024-12-11T00:05:10Z |
| format | Article |
| id | doaj.art-6d93860b22b4413dab7999f3770db9b0 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T00:05:10Z |
| publishDate | 2012-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-6d93860b22b4413dab7999f3770db9b02022-12-22T01:28:20ZengElsevierCell Reports2211-12472012-11-01251461147010.1016/j.celrep.2012.08.037Programmed Cell-to-Cell Variability in Ras Activity Triggers Emergent Behaviors during Mammary Epithelial MorphogenesisJennifer S. Liu0Justin T. Farlow1Amanda K. Paulson2Mark A. Labarge3Zev J. Gartner4Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USADepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USADepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USALife Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USADepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USAVariability in signaling pathway activation between neighboring epithelial cells can arise from local differences in the microenvironment, noisy gene expression, or acquired genetic changes. To investigate the consequences of this cell-to-cell variability in signaling pathway activation on coordinated multicellular processes such as morphogenesis, we use DNA-programmed assembly to construct three-dimensional MCF10A microtissues that are mosaic for low-level expression of activated H-Ras. We find two emergent behaviors in mosaic microtissues: cells with activated H-Ras are basally extruded or lead motile multicellular protrusions that direct the collective motility of their wild-type neighbors. Remarkably, these behaviors are not observed in homogeneous microtissues in which all cells express the activated Ras protein, indicating that heterogeneity in Ras activity, rather than the total amount of Ras activity, is critical for these processes. Our results directly demonstrate that cell-to-cell variability in pathway activation within local populations of epithelial cells can drive emergent behaviors during epithelial morphogenesis.http://www.sciencedirect.com/science/article/pii/S2211124712002781 |
| spellingShingle | Jennifer S. Liu Justin T. Farlow Amanda K. Paulson Mark A. Labarge Zev J. Gartner Programmed Cell-to-Cell Variability in Ras Activity Triggers Emergent Behaviors during Mammary Epithelial Morphogenesis Cell Reports |
| title | Programmed Cell-to-Cell Variability in Ras Activity Triggers Emergent Behaviors during Mammary Epithelial Morphogenesis |
| title_full | Programmed Cell-to-Cell Variability in Ras Activity Triggers Emergent Behaviors during Mammary Epithelial Morphogenesis |
| title_fullStr | Programmed Cell-to-Cell Variability in Ras Activity Triggers Emergent Behaviors during Mammary Epithelial Morphogenesis |
| title_full_unstemmed | Programmed Cell-to-Cell Variability in Ras Activity Triggers Emergent Behaviors during Mammary Epithelial Morphogenesis |
| title_short | Programmed Cell-to-Cell Variability in Ras Activity Triggers Emergent Behaviors during Mammary Epithelial Morphogenesis |
| title_sort | programmed cell to cell variability in ras activity triggers emergent behaviors during mammary epithelial morphogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2211124712002781 |
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