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Tissue Geometry Determines Sites of Mammary Branching Morphogenesis in Organotypic Cultures
Celeste M. Nelson,1*Martijn M. VanDuijn,3Jamie L. Inman,1Daniel A. Fletcher,2,3Mina J. Bissell1*
The treelike structures of many organs, including the mammarygland, are generated by branching morphogenesis, a reiterativeprocess of branch initiation and invasion from a preexistingepithelium. Using a micropatterning approach to control theinitial three-dimensional structure of mouse mammary epithelialtubules in culture, combined with an algorithm to quantify theextent of branching, we found that the geometry of tubules dictatesthe position of branches. We predicted numerically and confirmexperimentally that branches initiate at sites with a localminimum in the concentration of autocrine inhibitory morphogens,such as transforming growth factor–ß. Theseresults reveal that tissue geometry can control organ morphogenesisby defining the local cellular microenvironment, a finding thathas relevance to control of invasion and metastasis.
1 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. 2 Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. 3 Department of Bioengineering, University of California, Berkeley, CA 94720, USA.
* To whom correspondence should be addressed. E-mail: mjbissell{at}lbl.gov (M.J.B.); cmnelson{at}lbl.gov (C.M.N.)
Structural coupling of cardiomyocytes and noncardiomyocytes: quantitative comparisons using a novel micropatterned cell pair assay.
D. M. Pedrotty, R. Y. Klinger, N. Badie, S. Hinds, A. Kardashian, and N. Bursac (2008)
Am J Physiol Heart Circ Physiol
295, H390-H400
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