Kruppel-like factor 5 controls villus formation and initiation of cytodifferentiation in the embryonic intestinal epithelium.
Kruppel-like factor 5 controls villus formation and initiation of cytodifferentiation in the embryonic intestinal epithelium.
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DOI：
10.1016/j.ydbio.2012.12.010
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发表时间：
2013-03-15
影响因子：
2.7
通讯作者：
Whitsett, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Bell, Sheila M.;Zhang, Liqian;Xu, Yan;Besnard, Valerie;Wert, Susan E.;Shroyer, Noah;Whitsett, Jeffrey A.
Kruppel样因子5（Klf 5）是由形成胃肠道衬里的胚胎内胚层祖细胞表达的转录因子。Klf 5 floxed等位基因被有效地删除从肠上皮细胞的Cre转基因的Shh启动子的控制下，导致绒毛形态发生和上皮分化的抑制。尽管肠上皮细胞的增殖得以维持，但在Klf 5缺陷肠中，Elf 3、Pparγ、Atoh 1、Ascl 2、Neurog 3、Hnf 4 α、Cdx 1和其他与上皮细胞分化相关的基因的表达受到抑制。在E18.5时，Klf 5 Δ/Δ胎仔缺乏肠细胞的顶端刷状缘特征，观察到杯状细胞和肠内分泌细胞丢失。未能形成绒毛不是由于缺乏HH或PDGF信号传导，这一发育过程的已知介质。Klf 5-缺失阻断了FoxA 1和Sox 9表达的减少，这伴随着正常的绒毛形态发生。KLF 5直接抑制FoxA 1启动子的活性，反过来FOXA 1在体外抑制Elf 3基因表达，将观察到的Elf 3缺失与Klf 5缺陷小鼠中观察到的FoxA 1持续表达联系起来。遗传网络分析表明KLF 5是调控肠细胞分化和细胞粘附的关键转录因子。这些研究表明KLF 5启动早期内胚层的形态发生成为由绒毛和终末分化细胞组成的区室化肠上皮的新要求。
Kruppel-like factor 5 (Klf5) is a transcription factor expressed by embryonic endodermal progenitors that form the lining of the gastrointestinal tract. A Klf5 floxed allele was efficiently deleted from the intestinal epithelium by a Cre transgene under control of the Shh promoter resulting in the inhibition of villus morphogenesis and epithelial differentiation. Although proliferation of the intestinal epithelium was maintained, the expression of Elf3, Pparγ, Atoh1, Ascl2, Neurog3, Hnf4α, Cdx1, and other genes associated with epithelial cell differentiation was inhibited in the Klf5-deficient intestines. At E18.5, Klf5Δ/Δ fetuses lacked the apical brush border characteristic of enterocytes, and a loss of goblet and enteroendocrine cells was observed. The failure to form villi was not attributable to the absence of HH or PDGF signaling, known mediators of this developmental process. Klf5-deletion blocked the decrease in FoxA1 and Sox9 expression that accompanies normal villus morphogenesis. KLF5 directly inhibited activity of the FoxA1 promoter, and in turn FOXA1 inhibited Elf3 gene expression in vitro, linking the observed loss of Elf3 with the persistent expression of FoxA1 observed in Klf5-deficient mice. Genetic network analysis identified KLF5 as a key transcription factor regulating intestinal cell differentiation and cell adhesion. These studies indicate a novel requirement for KLF5 to initiate morphogenesis of the early endoderm into a compartmentalized intestinal epithelium comprised of villi and terminally differentiated cells.
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影响因子：
1.2
作者：
Besnard, V;Wert, SE;Whitsett, JA
通讯作者：
Whitsett, JA
影响因子：
5.2
作者：
Heanue, Tiffany A.;Pachnis, Vassilis
通讯作者：
Pachnis, Vassilis
影响因子：
29.4
作者：
Kolterud A;Grosse AS;Zacharias WJ;Walton KD;Kretovich KE;Madison BB;Waghray M;Ferris JE;Hu C;Merchant JL;Dlugosz AA;Kottmann AH;Gumucio DL
通讯作者：
Gumucio DL
影响因子：
2.7
作者：
Hryniuk, Alexa;Grainger, Stephanie;Lohnes, David
通讯作者：
Lohnes, David
DOI：
10.1073/pnas.91.20.9426
发表时间：
1994-09-27
影响因子：
11.1
作者：
JARCHAU, T;HAUSLER, C;WALTER, U
通讯作者：
WALTER, U