TY - JOUR
T1 - Glomerular differentiation in p27 and p57 double-mutant metanephroi
AU - Tomari, Shinsuke
AU - Nagahama, Hiroyasu
AU - Shu, Yujing
AU - Hoshi, Sachi
AU - Nakayama, Keiko
AU - Nakayama, Keiichi I.
AU - Nagata, Michio
PY - 2002
Y1 - 2002
N2 - The cell cycle inhibitors p27 and p57 are initially concurrently expressed at a critical point of glomerulogenesis and podocyte differentiation. The present study generated mice lacking both p27 and p57, in order to investigate the synergistic roles of these molecules in glomerular differentiation. It appeared that p27 and p57 double-mutant mice died between E16.5 and E18.5, before glomerular differentiation can take place. We harvested E13.5 metanephroi to advance the glomerulogenesis in a metanephric organ culture. Metanephroi of double-mutant and wild-type mice showed no great difference in size and shape at harvest or after 6 days in culture. Histology and morphometry revealed that average glomerular size in metanephroi from double-mutant mice was significantly larger than those in any other mutants. Larger glomeruli in double-mutant metanephroi are composed of an increased number of podocytes. The glomeruli in the double-mutant metanephroi expressed synaptopodin and WT-1 with the same pattern and intensity as those found in wild type. In addition, electron micrography showed the presence of foot processes and slit membrane in podocytes in double mutant. Western blot analysis of metanephroi after 6 days in culture showed an up-regulation of p21 protein in p27 mutant and double-mutant, but not in p57 mutant metanephroi. These findings suggest that p27 and p57 are synergistically involved, in part, to determine the number, but not the differentiation, in podocytes.
AB - The cell cycle inhibitors p27 and p57 are initially concurrently expressed at a critical point of glomerulogenesis and podocyte differentiation. The present study generated mice lacking both p27 and p57, in order to investigate the synergistic roles of these molecules in glomerular differentiation. It appeared that p27 and p57 double-mutant mice died between E16.5 and E18.5, before glomerular differentiation can take place. We harvested E13.5 metanephroi to advance the glomerulogenesis in a metanephric organ culture. Metanephroi of double-mutant and wild-type mice showed no great difference in size and shape at harvest or after 6 days in culture. Histology and morphometry revealed that average glomerular size in metanephroi from double-mutant mice was significantly larger than those in any other mutants. Larger glomeruli in double-mutant metanephroi are composed of an increased number of podocytes. The glomeruli in the double-mutant metanephroi expressed synaptopodin and WT-1 with the same pattern and intensity as those found in wild type. In addition, electron micrography showed the presence of foot processes and slit membrane in podocytes in double mutant. Western blot analysis of metanephroi after 6 days in culture showed an up-regulation of p21 protein in p27 mutant and double-mutant, but not in p57 mutant metanephroi. These findings suggest that p27 and p57 are synergistically involved, in part, to determine the number, but not the differentiation, in podocytes.
KW - Cell cycle inhibitor
KW - Differentiation
KW - Knockout mice
KW - Organ culture
KW - Podocytes
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U2 - 10.1007/s00429-002-0274-5
DO - 10.1007/s00429-002-0274-5
M3 - Article
C2 - 12478365
AN - SCOPUS:0036460334
SN - 0340-2061
VL - 206
SP - 31
EP - 36
JO - Anatomy and Embryology
JF - Anatomy and Embryology
IS - 1-2
ER -