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首页> 外文期刊>Molecular and Cellular Biology >c-Myc Is Required for the Formation of Intestinal Crypts but Dispensable for Homeostasis of the Adult Intestinal Epithelium
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c-Myc Is Required for the Formation of Intestinal Crypts but Dispensable for Homeostasis of the Adult Intestinal Epithelium

机译：c-Myc是肠道隐窝形成所必需的，但对于成人肠道上皮的稳态是必不可少的

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In self-renewing tissues such as the skin epidermis and the bone marrow, Myc proteins control differentiation of stem cells and proliferation of progenitor cell types. In the epithelium of the small intestine, we show that c-Myc and N-Myc are expressed in a differential manner. Whereas c-Myc is expressed in the proliferating transient-amplifying compartment of the crypts, N-Myc is restricted to the differentiated villus epithelium and a single cell located near the crypt base. c-Myc has been implicated as a critical target of the canonical Wnt pathway, which is essential for formation and maintenance of the intestinal mucosa. To genetically assess the role of c-Myc during development and homeostasis of the mammalian intestine we induced deletion of the c-mycflox allele in the villi and intestinal stem cell-bearing crypts of juvenile and adult mice, via tamoxifen-induced activation of the CreERT2 recombinase, driven by the villin promoter. Absence of c-Myc activity in the juvenile mucosa at the onset of crypt morphogenesis leads to a failure to form normal numbers of crypts in the small intestine. However, all mice recover from this insult to form and maintain a normal epithelium in the absence of c-Myc activity and without apparent compensation by N-Myc or L-Myc. This study provides genetic and molecular evidence that proliferation and expansion of progenitors necessary to maintain the adult intestinal epithelium can unexpectedly occur in a Myc-independent manner.
机译：在自我更新的组织（例如皮肤表皮和骨​​髓）中，Myc蛋白控制干细胞的分化和祖细胞类型的增殖。在小肠的上皮中，我们显示c-Myc和N-Myc以差异的方式表达。尽管c-Myc在隐窝的增殖瞬变放大区室中表达，但N-Myc限于分化的绒毛上皮和位于隐窝碱基附近的单个细胞。 c-Myc被认为是经典Wnt途径的关键靶点，这对于形成和维持肠粘膜至关重要。为了从遗传角度评估c-Myc在哺乳动物小肠发育和体内稳态中的作用，我们在绒毛和带有肠干细胞的动物中诱导了c- myc flox 等位基因的缺失通过他莫昔芬诱导的由villin启动子驱动的CreER T2 重组酶的激活来激活幼鼠和成年小鼠的隐窝隐窝形态发生开始时少年黏膜中c-Myc活性的缺乏导致无法在小肠中形成正常数目的隐窝。但是，所有小鼠均从这种损伤中恢复，在没有c-Myc活性且没有明显的N-Myc或L-Myc补偿的情况下形成并维持正常的上皮。这项研究提供了遗传和分子证据，表明维持成年肠道上皮细胞所必需的祖细胞的增殖和扩增可能会以Myc独立的方式意外发生。

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