Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures

被引:465
作者
Nelson, Celeste M.
VanDuijn, Martijn M.
Inman, Jamie L.
Fletcher, Daniel A.
Bissell, Mina J. [1 ]
机构
[1] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA 94720 USA
[3] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA
关键词
D O I
10.1126/science.1131000
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The treelike structures of many organs, including the mammary gland, are generated by branching morphogenesis, a reiterative process of branch initiation and invasion from a preexisting epithelium. Using a micropatterning approach to control the initial three-dimensional structure of mouse mammary epithelial tubules in culture, combined with an algorithm to quantify the extent of branching, we found that the geometry of tubules dictates the position of branches. We predicted numerically and confirm experimentally that branches initiate at sites with a local minimum in the concentration of autocrine inhibitory morphogens, such as transforming growth factor - beta. These results reveal that tissue geometry can control organ morphogenesis by defining the local cellular microenvironment, a finding that has relevance to control of invasion and metastasis.
引用
收藏
页码:298 / 300
页数:3
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