The Ets transcription factor Elf5 specifies mammary alveolar cell fate.
Hormonal cues regulate mammary development, but the consequent transcriptional changes and cell fate decisions are largely undefined. We show that knockout of the prolactin-regulated Ets transcription factor Elf5 prevented formation of the secretory epithelium during pregnancy. Conversely, overexpression of Elf5 in an inducible transgenic model caused alveolar differentiation and milk secretion in virgin mice, disrupting ductal morphogenesis. CD61+ luminal progenitor cells accumulated in Elf5-deficient mammary glands and were diminished in glands with Elf5 overexpression. Thus Elf5 specifies the differentiation of CD61+ progenitors to establish the secretory alveolar lineage during pregnancy, providing a link between prolactin, transcriptional events, and alveolar development.
Oakes
Samantha R
SR
Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
Naylor
Matthew J
MJ
Asselin-Labat
Marie-Liesse
ML
Blazek
Katrina D
KD
Gardiner-Garden
Margaret
M
Hilton
Heidi N
HN
Kazlauskas
Michael
M
Pritchard
Melanie A
MA
Chodosh
Lewis A
LA
Pfeffer
Peter L
PL
Lindeman
Geoffrey J
GJ
Visvader
Jane E
JE
Ormandy
Christopher J
CJ
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D005260:Female; D039661:Integrin beta3 / Q000032:analysis; D007774:Lactation / Q000235:genetics*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics*; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C500759:Elf5 protein, mouse; D039661:Integrin beta3; D014157:Transcription Factors