Paracrine Hedgehog signaling in stomach and intestine: new roles for hedgehog in gastrointestinal patterning.
Paracrine Hedgehog signaling in stomach and intestine: new roles for hedgehog in gastrointestinal patterning.
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DOI：
10.1053/j.gastro.2009.05.002
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发表时间：
2009-08
期刊：
影响因子：
29.4
通讯作者：
Gumucio DL
中科院分区：
文献类型：
--
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
Hedgehog信号传导在胃肠道模式中至关重要。Hedgehog信号传导缺陷的小鼠表现出反映在人VEGIL（脊椎、肛门、心脏、气管、食道、肾脏、肢体）联合中观察到的畸形的异常。然而，Hedgehog信号流的方向是有争议的，Hedgehog信号传导的细胞靶点在发育过程中随着时间的推移而变化。我们分析了从胚胎10.5天（E10.5）到成年小鼠胃窦，幽门区，小肠和结肠的细胞Hedgehog反应模式。使用Hedgehog通路报告小鼠和原位杂交分析Hedgehog信号传导。通过免疫染色鉴定细胞靶点。产生并分析过表达ihh的转基因动物。从胚胎期到成年期，Hedgehog信号从胃窦到结肠都是严格的旁分泌。新发现包括：浆膜间皮细胞在胎儿期发出Hedgehog信号; E10.5时后肠上皮表达Ptch但不表达Gli 1;两层外肌层对Hedgehog信号的反应不同;幽门括约肌的器官发生与强大的Hedgehog信号相关; E16时胃和肠的Hedgehog反应显著不同;出生后，粘膜肌层和绒毛平滑肌（SM）主要由Hedgehog反应细胞组成，Hh水平主动调节绒毛核心SM。这些研究揭示了一个以前未被认识到的关联旁分泌刺猬信号与几个胃肠道模式的事件，涉及浆膜，幽门和绒毛平滑肌。这些结果可能对几种人类异常产生影响，并可能扩大人类VEGIL关联的范围。
Hedgehog signaling is critical in gastrointestinal patterning. Mice deficient in Hedgehog signaling exhibit abnormalities that mirror deformities seen in the human VACTERL (vertebral, anal, cardiac, tracheal, esophageal, renal, limb) association. However, the direction of Hedgehog signal flow is controversial and the cellular targets of Hedgehog signaling change with time during development. We profiled cellular Hedgehog response patterns from embryonic day 10.5 (E10.5) to adult in murine antrum, pyloric region, small intestine and colon. Hedgehog signaling was profiled using Hedgehog pathway reporter mice and in situ hybridization. Cellular targets were identified by immunostaining. Ihh-overexpressing transgenic animals were generated and analyzed. Hedgehog signaling is strictly paracrine from antrum to colon throughout embryonic and adult life. Novel findings include: mesothelial cells of the serosa transduce Hedgehog signals in fetal life; the hindgut epithelium expresses Ptch but not Gli1 at E10.5; the two layers of the muscularis externa respond differently to Hedgehog signals; organogenesis of the pyloric sphincter is associated with robust Hedgehog signaling; dramatically different Hedgehog responses characterize stomach and intestine at E16; after birth, the muscularis mucosa and villus smooth muscle (SM) consist primarily of Hedgehog responsive cells and Hh levels actively modulate villus core SM. These studies reveal a previously unrecognized association of paracrine Hedgehog signaling with several gastrointestinal patterning events involving the serosa, pylorus and villus smooth muscle. The results may have implications for several human anomalies and could potentially expand the spectrum of the human VACTERL association.
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影响因子：
2.4
作者：
DICKSON, JAS
通讯作者：
DICKSON, JAS
影响因子：
5
作者：
Hernanz-Schulman, M;Lowe, LH;Cywes, R
通讯作者：
Cywes, R
影响因子：
3.8
作者：
Kansu, A;Ensari, A;Girgin, N
通讯作者：
Girgin, N
影响因子：
5
作者：
MAGILNER, AD
通讯作者：
MAGILNER, AD
影响因子：
4.8
作者：
Madison, BB;Dunbar, L;Gumucio, DL
通讯作者：
Gumucio, DL