Bmp signaling is required for intestinal growth and morphogenesis
Bmp signaling is required for intestinal growth and morphogenesis
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DOI：
10.1002/dvdy.20741
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发表时间：
2006-06-01
影响因子：
2.5
通讯作者：
Kulessa, Holger
中科院分区：
文献类型：
--
作者：
Batts, Lorene E.;Polk, D. Brent;Kulessa, Holger
肠的生长、形态发生、分化和稳态是由上皮细胞和下层间充质基质之间的相互作用调节的。幼年型息肉病患者BMPR1A突变的鉴定暗示Bmp信号传导是这些相互作用的重要介质。为了验证这一假设，我们抑制BMP信号在小鼠近端肠道的BMP拮抗剂，头蛋白，使用脂肪酸结合蛋白（Fabp 1）基因的调控元件的转基因错误表达。这导致异常绒毛形态发生、间质和上皮增生以及异位隐窝形成。由此产生的肠组织病理学类似于在人类幼年性息肉病中所见。头蛋白在大肠中的错误表达在肠道的该区域中产生类似的异常表型。对转基因小肠中基因表达的分析提出了Hedgehog和Pdgf信号传导在幼年型息肉样表型的发展中发挥作用的可能性。
Intestinal growth, morphogenesis, differentiation, and homeostasis are regulated by reciprocal interactions between the epithelium and the underlying mesenchymal stroma. The identification of BMPR1A mutations in patients with Juvenile Polyposis implicates Bmp signaling as an important mediator of these interactions. To test this hypothesis, we inhibited Bmp signaling in the mouse proximal intestine by transgenic misexpression of the BMP antagonist, noggin, using regulatory elements of the fatty acid binding protein (Fabp1) gene. This leads to abnormal villus morphogenesis, stromal and epithelial hyperplasia, and ectopic crypt formation. The resulting intestinal histopathology resembles that seen in human Juvenile Polyposis. Misexpression of noggin in the large intestine gives a similar abnormal phenotype in this region of the gut. Analysis (of gene expression in the transgenic small intestine raises the possibility that Hedgehog and Pdgf signaling play a role in the development of the Juvenile Polyposis-like phenotype.