Wnt4 is not sufficient to induce lobuloalveolar mammary development.
BACKGROUND
Brisken et al (2000) showed that Wnt4 null mammary glands were deficient in early lobuloalveolar mammary outgrowth during pregnancy, and implicated Wnt4 as an effector for the progesterone-induced mammary growth program. Though ectopic Wnt1 signaling is known to be mitogenic and oncogenic, no endogenously expressed Wnt ligands have ever been directly implicated in mammary growth and morphogenesis. Therefore, we generated conditional transgenic mice to test whether Wnt4 can stimulate mammary epithelial cell growth.


RESULTS
We found that despite pregnancy-associated expression levels of Wnt4, mammary glands did not display the side-branching typical of early pregnancy. Control experiments designed to test the Wnt4 construct in zebrafish reproduced other studies that demonstrated Wnt4-specific phenotypes distinct from Wnt1-induced phenotypes. Indeed, using qPCR-based array analyses, we found that a specific transcriptional target of Wnt4, namely Wnt16, was induced in Wnt4-expressing transgenic glands, to levels equivalent to that of early pregnant glands.


CONCLUSIONS
Taken together, we propose that Wnt4 is necessary, but not sufficient, to induce side-branch development.
Kim
Young Chul
YC
McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin-Madison, Wisconsin, USA. yckim@oncology.wisc.edu
Clark
Rod J
RJ
Pelegri
Francisco
F
Alexander
Caroline M
CM
D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D013754:Tetracyclines / Q000494:pharmacology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D060528:Wnt4 Protein
D013754:Tetracyclines; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D008156:Luciferases; D004318:Doxycycline