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首页> 外文期刊>Development >Delta-Notch signalling controls commitment to a secretory fate in the zebrafish intestine.
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Delta-Notch signalling controls commitment to a secretory fate in the zebrafish intestine.

机译：Delta-Notch信号控制着对斑马鱼肠道中分泌命运的承诺。

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The transparency of the juvenile zebrafish and its genetic advantages make it an attractive model for study of cell turnover in the gut. BrdU labelling shows that the gut epithelium is renewed in essentially the same way as in mammals: the villi are lined with non-dividing differentiated cells, while cell division is confined to the intervillus pockets. New cells produced in the pockets take about 4 days to migrate out to the tips of the villi, where they die. We have generated monoclonal antibodies to identify the absorptive and secretory cells in the epithelium, and we have used these antibodies to examine the part that Delta-Notch signalling plays in producing the diversity of intestinal cell types. Several Notch receptors and ligands are expressed in the gut. In particular, the Notch ligand DeltaD (Delta1 in the mouse) is expressed in cells of the secretory lineage. In an aei mutant, where DeltaD is defective, secretory cells are overproduced. In mind bomb (mib), where all Delta-Notch signalling isbelieved to be blocked, almost all the cells in the 3-day gut epithelium adopt a secretory character. Thus, secretory differentiation appears to be the default in the absence of Notch activation, and lateral inhibition mediated by Delta-Notch signalling is required to generate a balanced mixture of absorptive and secretory cells. These findings demonstrate the central role of Notch signalling in the gut stem-cell system and establish the zebrafish as a model for study of the mechanisms controlling renewal of gut epithelium.
机译：斑马鱼的透明性及其遗传优势使其成为研究肠道细胞更新的有吸引力的模型。 BrdU标记显示，肠道上皮的更新与哺乳动物基本相同：绒毛衬有未分裂的分化细胞，而细胞分裂则局限于间质囊。口袋中产生的新细胞大约需要4天才能迁移到绒毛尖端，并在那里死亡。我们已经生成了单克隆抗体来识别上皮中的吸收性细胞和分泌性细胞，并且我们已使用这些抗体来检查Delta-Notch信号在产生肠道细胞类型多样性中所起的作用。几种Notch受体和配体在肠道中表达。特别是，Notch配体DeltaD（在小鼠中为Delta1）在分泌谱系的细胞中表达。在DeltaD有缺陷的aei突变体中，分泌细胞过度产生。在炸弹（mib）中，认为所有Delta-Notch信号均被阻断，在3天的肠道上皮细胞中几乎所有细胞都具有分泌特性。因此，在没有Notch激活的情况下，分泌分化似乎是默认的，并且需要由Delta-Notch信号传导介导的侧向抑制才能产生吸收性和分泌性细胞的平衡混合物。这些发现证明了Notch信号在肠道干细胞系统中的核心作用，并建立了斑马鱼作为模型来研究控制肠道上皮更新的机制。

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