Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling.
Female reproductive hormones control mammary gland morphogenesis. In the absence of the progesterone receptor (PR) from the mammary epithelium, ductal side-branching fails to occur. We can overcome this defect by ectopic expression of the protooncogene Wnt-1. Transplantation of mammary epithelia from Wnt-4(-)/(-) mice shows that Wnt-4 has an essential role in side-branching early in pregnancy. PR and Wnt-4 mRNAs colocalize to the luminal compartment of the ductal epithelium. Progesterone induces Wnt-4 in mammary epithelial cells and is required for increased Wnt-4 expression during pregnancy. Thus, Wnt signaling is essential in mediating progesterone function during mammary gland morphogenesis.
Brisken
C
C
Department of Molecular and Integrative Physiology, Whitehead Institute, Cambridge, Massachusetts 02142 USA.
Heineman
A
A
Chavarria
T
T
Elenbaas
B
B
Tan
J
J
Dey
S K
SK
McMahon
J A
JA
McMahon
A P
AP
Weinberg
R A
RA
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008321:Mammary Glands, Animal / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D011374:Progesterone / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015347:RNA Probes; D011980:Receptors, Progesterone / Q000235:genetics; D015398:Signal Transduction; D051153:Wnt Proteins; D060528:Wnt4 Protein
D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D015347:RNA Probes; D011980:Receptors, Progesterone; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D011374:Progesterone