TY - JOUR
T1 - Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures
AU - Nelson, Celeste M.
AU - VanDuijn, Martijn M.
AU - Inman, Jamie L.
AU - Fletcher, Daniel A.
AU - Bissell, Mina J.
PY - 2006/10/13
Y1 - 2006/10/13
N2 - 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-β. 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.
AB - 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-β. 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.
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U2 - 10.1126/science.1131000
DO - 10.1126/science.1131000
M3 - Article
C2 - 17038622
AN - SCOPUS:33749992857
SN - 0036-8075
VL - 314
SP - 298
EP - 300
JO - Science
JF - Science
IS - 5797
ER -