Self-organization of engineered epithelial tubules by differential cellular motility.
Patterning of developing tissues arises from a number of mechanisms, including cell shape change, cell proliferation, and cell sorting from differential cohesion or tension. Here, we reveal that differences in cell motility can also lead to cell sorting within tissues. Using mosaic engineered mammary epithelial tubules, we found that cells sorted depending on their expression level of the membrane-anchored collagenase matrix metalloproteinase (MMP)-14. These rearrangements were independent of the catalytic activity of MMP14 but absolutely required the hemopexin domain. We describe a signaling cascade downstream of MMP14 through Rho kinase that allows cells to sort within the model tissues. Cell speed and persistence time were enhanced by MMP14 expression, but only the latter motility parameter was required for sorting. These results indicate that differential directional persistence can give rise to patterns within model developing tissues.
Mori
Hidetoshi
H
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Gjorevski
Nikolce
N
Inman
Jamie L
JL
Bissell
Mina J
MJ
Nelson
Celeste M
CM
D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology* / Q000201:enzymology; D005260:Female; D006466:Hemopexin / Q000235:genetics / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000201:enzymology; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D046509:Tissue Culture Techniques / Q000379:methods*; D054460:rho-Associated Kinases / Q000378:metabolism
D006466:Hemopexin; D054460:rho-Associated Kinases; D053511:Matrix Metalloproteinase 14
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