Roles of BMP signaling and Nkx2.5 in patterning at the chick midgut-foregut boundary.
Roles of BMP signaling and Nkx2.5 in patterning at the chick midgut-foregut boundary.
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DOI：
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发表时间：
2000-09
期刊：
影响因子：
4.6
通讯作者：
Devyn M. Smith;Corinne M. Nielsen;C. Tabin;D. Roberts
中科院分区：
文献类型：
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作者：
Devyn M. Smith;Corinne M. Nielsen;C. Tabin;D. Roberts
肠道形成形态上不同的区域是由于适当的因子以严格的空间和时间模式表达，以分配细胞在发育中的命运。通常，发育早期基因表达的边界对应于成年肠道不同区域之间的划分。例如，Bmp4在整个后肠和中肠中表达，但在早期砂囊中不表达。异位BMP 4在砂囊引起肌层变薄。为了理解这种表型，我们研究了在肠道发育过程中转导BMP信号的受体的表达。我们发现BMP受体在鸡胚胎肠道的不同区域有差异表达。通过使用BMP I型受体的组成型激活版本，我们发现BMP受体在异位表达时与砂囊中的BMP 4起类似的作用。我们发现，异位BMP信号传导后看到的中胚层变薄是由于细胞凋亡的增加和砂囊中胚层内增殖的减少。中胚层变薄的特征是肌胃中胚层平滑肌的紊乱和缺乏分化。此外，异位BMP受体导致幽门括约肌标记物Nkx2.5上调，与异位BMP 4中观察到的情况类似。这种Nkx2.5的上调是砂囊中胚层内的细胞自主事件。我们还发现Nkx2.5是建立幽门括约肌分化方面的必要和充分的。
Patterning of the gut into morphologically distinct regions results from the appropriate factors being expressed in strict spatial and temporal patterns to assign cells their fates in development. Often, the boundaries of gene expression early in development correspond to delineations between different regions of the adult gut. For example, Bmp4 is expressed throughout the hindgut and midgut, but is not expressed in the early gizzard. Ectopic BMP4 in the gizzard caused a thinning of the muscularis. To understand this phenotype we examined the expression of the receptors transducing BMP signaling during gut development. We find that the BMP receptors are differentially expressed in distinct regions of the chicken embryonic gut. By using constitutively activated versions of the BMP type I receptors, we find that the BMP receptors act similarly to BMP4 in the gizzard when ectopically expressed. We show that the mesodermal thinning seen upon ectopic BMP signaling is due to an increase in apoptosis and a decrease in proliferation within the gizzard mesoderm. The mesodermal thinning is characterized by a disorganization and lack of differentiation of smooth muscle in the gizzard mesoderm. Further, ectopic BMP receptors cause an upregulation of Nkx2.5, the pyloric sphincter marker, similar to that seen with ectopic BMP4. This upregulation of Nkx2.5 is a cell-autonomous event within the mesoderm of the gizzard. We also find that Nkx2.5 is necessary and sufficient for establishing aspects of pyloric sphincter differentiation.