Self-organization of engineered epithelial tubules by differential cellular motility
- Hidetoshi Moria,1,
- Nikolce Gjorevskib,1,
- Jamie L. Inmana,1,
- Mina J. Bissella,2 and
- Celeste M. Nelsonb,2
- aLife Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720; and
- bDepartments of Chemical Engineering and Molecular Biology, Princeton University, Princeton, NJ 08544
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Edited by Kenneth Yamada, National Institutes of Health, Bethesda, MD, and accepted by the Editorial Board July 16, 2009
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↵1H.M., N.G., and J.L.I. contributed equally to this work. (received for review February 4, 2009)
Abstract
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.
Footnotes
- 2To whom correspondence may be addressed. E-mail: celesten{at}princeton.edu or mjbissell{at}lbl.gov
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Author contributions: M.J.B. and C.M.N. designed research; H.M., N.G., J.L.I., and C.M.N. performed research; N.G. and C.M.N. analyzed data; and C.M.N. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission. K.Y. is a guest editor invited by the Editorial Board.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0901269106/DCSupplemental.
