Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10585-90. doi: 10.1073/pnas.1105852108. Epub 2011 Jun 13.
Female mammals produce milk to feed their newborn offspring before teeth develop and permit the consumption of solid food. Intestinal enterocytes dramatically alter their biochemical signature during the suckling-to-weaning transition. The transcriptional repressor Blimp1 is strongly expressed in immature enterocytes in utero, but these are gradually replaced by Blimp1(-) crypt-derived adult enterocytes. Here we used a conditional inactivation strategy to eliminate Blimp1 function in the developing intestinal epithelium. There was no noticeable effect on gross morphology or formation of mature cell types before birth. However, survival of mutant neonates was severely compromised. Transcriptional profiling experiments reveal global changes in gene expression patterns. Key components of the adult enterocyte biochemical signature were substantially and prematurely activated. In contrast, those required for processing maternal milk were markedly reduced. Thus, we conclude Blimp1 governs the developmental switch responsible for postnatal intestinal maturation.
雌性哺乳动物在牙齿发育并允许食用固体食物之前，会分泌乳汁来喂养新生幼崽。在哺乳到断奶的过渡期间，肠道肠细胞会剧烈改变其生化特征。转录抑制因子 Blimp1 在子宫内未成熟的肠细胞中强烈表达，但这些细胞逐渐被 Blimp1(-)隐窝衍生的成年肠细胞取代。在这里，我们使用条件性失活策略来消除发育中的肠上皮细胞中的 Blimp1 功能。在出生前，对大体形态或成熟细胞类型的形成没有明显影响。然而，突变幼仔的存活率严重受损。转录谱实验揭示了基因表达模式的全局变化。成年肠细胞生化特征的关键组成部分被大量且过早地激活。相比之下，那些用于处理母体乳汁的成分则明显减少。因此，我们得出结论，Blimp1 控制着负责出生后肠道成熟的发育开关。
