Colony stimulating factor-1 is required to recruit macrophages into the mammary gland to facilitate mammary ductal outgrowth.
Mammary gland development initiates postnatally with the development of terminal end buds (TEBs) at the end of the rudimentary ducts. These grow out through the fat pad and bifurcate to lay down the rudimentary ductal tree. At the initiation of their development, TEBs recruit to their surrounding stroma a substantial population of macrophages. Using mice homozygous for a null mutation in the gene for the macrophage growth factor, colony stimulating factor-1 (CSF-1), that are severely depleted in macrophages, we demonstrated that CSF-1-regulated macrophages are required for normal branching morphogenesis in the mammary gland. However, these mice have a pleiotropic phenotype as a result of the generalized macrophage deficiency. To test that the effect of the mutation observed in the mammary gland was organ-autonomous, we developed a tetracycline-binary system whereby CSF-1 was specifically expressed in the mammary epithelium under the regulation of the MMTV-promoter. This restored mammary macrophage populations but not those in other tissues and corrected the branching morphogenesis defect. Inhibition of CSF-1 expression by tetracycline treatment for varying periods suggested that CSF-1-regulated macrophages are required throughout early mammary gland development. These data show that macrophages acting locally are required for branching morphogenesis of the mammary gland.
Van Nguyen
Andrew
A
Department of Developmental and Molecular Biology, Center for the Study of Reproductive Biology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park, New York, New York, 10461, USA.
Pollard
Jeffrey W
JW
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D005260:Female; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D009154:Mutation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013752:Tetracycline / Q000494:pharmacology
D011500:Protein Synthesis Inhibitors; D016173:Macrophage Colony-Stimulating Factor; D013752:Tetracycline