Coordinate integrin and c-Met signaling regulate Wnt gene expression during epithelial morphogenesis.
Integrin receptors for the extracellular matrix and receptor tyrosine kinase growth factor receptors represent two of the major families of receptors that transduce into cells information about the surrounding environment. Wnt proteins are a major family of signaling molecules that regulate morphogenetic events. There is presently little understanding of how the expression of Wnt genes themselves is regulated. In this study, we demonstrate that alpha3beta1 integrin, a major laminin receptor involved in the development of the kidney, and c-Met, the receptor for hepatocyte growth factor, signal coordinately to regulate the expression of Wnt7b in the mouse. Wnt signals in turn appear to regulate epithelial cell survival in the papilla of the developing kidney, allowing for the elongation of epithelial tubules to form a mature papilla. Together, these results demonstrate how signals from integrins and growth factor receptors can be integrated to regulate the expression of an important family of signaling molecules so as to regulate morphogenetic events.
Liu
Yingjie
Y
Department of Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Chattopadhyay
Nibedita
N
Qin
Shan
S
Szekeres
Charles
C
Vasylyeva
Tetyana
T
Mahoney
Zhen X
ZX
Taglienti
Mary
M
Bates
Carlton M
CM
Chapman
Harold A
HA
Miner
Jeffrey H
JH
Kreidberg
Jordan A
JA
D000818:Animals; D001483:Base Sequence; D002470:Cell Survival; D017931:DNA Primers / Q000235:genetics; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D039201:Integrin alpha3beta1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D007797:Laminin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
D017931:DNA Primers; D039201:Integrin alpha3beta1; D007797:Laminin; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C095937:Wnt7b protein, mouse; C097043:laminin alpha5; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met