Loss of transcription factor AP-2gamma/TFAP2C impairs branching morphogenesis of the murine mammary gland.
Extensive development of the mammary gland occurs during puberty, when rising levels of ovarian hormones induce the formation of highly proliferative terminal end buds (TEBs) at the tips of mammary ducts. TEBs consist of an outer layer of cap cells and of inner body cells. TEBs invade the adipose stroma and bifurcate while extending the ducts to generate an arborized ductal network. We show that in murine mammary glands transcription factor AP-2gamma is strongly expressed in the cap cell layer and in a subset of body cells of TEBs. To decipher AP-2gamma functions during mammary development we generated AP-2gamma-deficient mice. Their mammary glands displayed impaired ductal branching and elongation. Cellular proliferation within TEBs was reduced. Although estrogen receptor was expressed, exogenously administered ovarian hormones could not restore normal development. Therefore, AP-2gamma is functionally involved in branching morphogenesis of the mammary epithelium, possibly by controlling genetic processes downstream of ovarian hormones.
Institute for Pathology, Department of Developmental Pathology, University of Bonn Medical School, Bonn, Germany.
Richard
R
Jäger
Sabine
S
Schäfer
Mathilde
M
Hau-Liersch
Hubert
H
Schorle
D000818:Animals; D049109:Cell Proliferation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009024:Morphogenesis; D010053:Ovary / Q000254:growth & development* / Q000378:metabolism; D010641:Phenotype; D011960:Receptors, Estrogen / Q000378:metabolism; D050656:Transcription Factor AP-2 / Q000096:biosynthesis*; D014157:Transcription Factors / Q000378:metabolism
D011960:Receptors, Estrogen; D050656:Transcription Factor AP-2; D014157:Transcription Factors