Oakes Samantha R, Naylor Matthew J, Asselin-Labat Marie-Liesse, Blazek Katrina D, Gardiner-Garden Margaret, Hilton Heidi N, Kazlauskas Michael, Pritchard Melanie A, Chodosh Lewis A, Pfeffer Peter L, Lindeman Geoffrey J, Visvader Jane E, Ormandy Christopher J
Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
Genes Dev. 2008 Mar 1;22(5):581-6. doi: 10.1101/gad.1614608.
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.
激素信号调节乳腺发育，但其后续的转录变化和细胞命运决定在很大程度上尚不明确。我们发现，催乳素调节的Ets转录因子Elf5基因敲除会阻止孕期分泌上皮的形成。相反，在可诱导转基因模型中过表达Elf5会导致处女鼠出现肺泡分化和乳汁分泌，扰乱导管形态发生。CD61+管腔祖细胞在Elf5缺陷的乳腺中积累，而在Elf5过表达的腺体中减少。因此，Elf5决定了CD61+祖细胞的分化，以在孕期建立分泌性肺泡谱系，为催乳素、转录事件和肺泡发育之间提供了联系。
