Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Development. 2012 Sep;139(17):3147-56. doi: 10.1242/dev.079616. Epub 2012 Jul 25.
Mammary epithelial cells undergo structural and functional differentiation at late pregnancy and parturition to produce and secrete milk. Both TGF-β and prolactin pathways are crucial regulators of this process. However, how the activities of these two antagonistic pathways are orchestrated to initiate lactation has not been well defined. Here, we show that SnoN, a negative regulator of TGF-β signaling, coordinates TGF-β and prolactin signaling to control alveologenesis and lactogenesis. SnoN expression is induced at late pregnancy by the coordinated actions of TGF-β and prolactin. The elevated SnoN promotes Stat5 signaling by enhancing its stability, thereby sharply increasing the activity of prolactin signaling at the onset of lactation. SnoN-/- mice display severe defects in alveologenesis and lactogenesis, and mammary epithelial cells from these mice fail to undergo proper morphogenesis. These defects can be rescued by an active Stat5. Thus, our study has identified a new player in the regulation of milk production and revealed a novel function of SnoN in mammary alveologenesis and lactogenesis in vivo through promotion of Stat5 signaling.
乳腺上皮细胞在妊娠晚期和分娩时经历结构和功能分化，以产生和分泌乳汁。TGF-β和催乳素途径都是这个过程的关键调节因子。然而，这两种拮抗途径的活性如何协调启动泌乳还没有很好地定义。在这里，我们表明，SnoN，TGF-β 信号的负调节剂，协调 TGF-β 和催乳素信号来控制肺泡发生和泌乳发生。SnoN 的表达在妊娠晚期受到 TGF-β 和催乳素的协同作用诱导。升高的 SnoN 通过增强其稳定性来促进 Stat5 信号，从而在泌乳开始时急剧增加催乳素信号的活性。SnoN-/-小鼠在肺泡发生和泌乳发生方面表现出严重缺陷，并且来自这些小鼠的乳腺上皮细胞不能进行适当的形态发生。这些缺陷可以通过活性 Stat5 来挽救。因此，我们的研究鉴定了一个新的调节乳汁产生的因子，并通过促进 Stat5 信号揭示了 SnoN 在体内乳腺肺泡发生和泌乳发生中的新功能。
