TY - JOUR
T1 - Vertebrate kidney tubules elongate using a planar cell polarity-dependent, rosette-based mechanism of convergent extension
AU - Lienkamp, Soeren S.
AU - Liu, Kun
AU - Karner, Courtney M.
AU - Carroll, Thomas J.
AU - Ronneberger, Olaf
AU - Wallingford, John B.
AU - Walz, Gerd
PY - 2012/12
Y1 - 2012/12
N2 - Cystic kidney diseases are a global public health burden, affecting over 12 million people1. Although much is known about the genetics of kidney development and disease, the cellular mechanisms driving normal kidney tubule elongation remain unclear2,3. Here, we used in vivo imaging to show for the first time that mediolaterally oriented cell intercalation is fundamental to vertebrate kidney morphogenesis. Unexpectedly, we found that kidney tubule elongation is driven in large part by a myosin-dependent, multicellular rosette-based mechanism, previously only described in Drosophila melanogaster. In contrast to findings in Drosophila, however, non-canonical Wnt and planar cell polarity (PCP) signaling is required to control rosette topology and orientation during vertebrate kidney tubule elongation. These data resolve long-standing questions concerning the role of PCP signaling in the developing kidney and, moreover, establish rosette-based intercalation as a deeply conserved cellular engine for epithelial morphogenesis.
AB - Cystic kidney diseases are a global public health burden, affecting over 12 million people1. Although much is known about the genetics of kidney development and disease, the cellular mechanisms driving normal kidney tubule elongation remain unclear2,3. Here, we used in vivo imaging to show for the first time that mediolaterally oriented cell intercalation is fundamental to vertebrate kidney morphogenesis. Unexpectedly, we found that kidney tubule elongation is driven in large part by a myosin-dependent, multicellular rosette-based mechanism, previously only described in Drosophila melanogaster. In contrast to findings in Drosophila, however, non-canonical Wnt and planar cell polarity (PCP) signaling is required to control rosette topology and orientation during vertebrate kidney tubule elongation. These data resolve long-standing questions concerning the role of PCP signaling in the developing kidney and, moreover, establish rosette-based intercalation as a deeply conserved cellular engine for epithelial morphogenesis.
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U2 - 10.1038/ng.2452
DO - 10.1038/ng.2452
M3 - Article
C2 - 23143599
AN - SCOPUS:84870478180
SN - 1061-4036
VL - 44
SP - 1382
EP - 1387
JO - Nature genetics
JF - Nature genetics
IS - 12
ER -