The Ets transcription factor Elf5 specifies mammary alveolar cell fate

  1. Samantha R. Oakes1,7,
  2. Matthew J. Naylor1,2,7,
  3. Marie-Liesse Asselin-Labat3,
  4. Katrina D. Blazek1,
  5. Margaret Gardiner-Garden1,
  6. Heidi N. Hilton1,
  7. Michael Kazlauskas1,
  8. Melanie A. Pritchard4,
  9. Lewis A. Chodosh5,
  10. Peter L. Pfeffer6,
  11. Geoffrey J. Lindeman3,
  12. Jane E. Visvader3, and
  13. Christopher J. Ormandy1,2,8
  1. 1 Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia;
  2. 2 St. Vincent’s Hospital Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2052, Australia;
  3. 3 Victorian Breast Cancer Research Consortium (VBCRC) Laboratory, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia;
  4. 4 Centre for Functional Genomics and Human Disease, Monash Institute of Medical Research, Clayton, Victoria 3168, Australia;
  5. 5 Department of Cancer Biology and Abramson Family Cancer Research Institute, University of Pennslvania, Philadelphia, Pennsylvania 19104, USA;
  6. 6 AgResearch Ruakura, Hamilton 3240, New Zealand

  1. ↵7 These authors contributed equally to this work.

Abstract

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.

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  1. doi: 10.1101/gad.1614608 Genes & Dev. 22: 581-586 Copyright © 2008, Cold Spring Harbor Laboratory Press

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