Gastrointestinal defects of the Gas1 mutant involve dysregulated Hedgehog and Ret signaling.
Gastrointestinal defects of the Gas1 mutant involve dysregulated Hedgehog and Ret signaling.
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DOI：
10.1242/bio.20123186
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发表时间：
2013-02-15
期刊：
影响因子：
2.4
通讯作者：
Fan CM
中科院分区：
文献类型：
--
作者：
Biau S;Jin S;Fan CM
The gastrointestinal (GI) tract defines the digestive system and is composed of the stomach, intestine and colon. Among the major cell types lining radially along the GI tract are the epithelium, mucosa, smooth muscles and enteric neurons. The Hedgehog (Hh) pathway has been implicated in directing various aspects of the developing GI tract, notably the mucosa and smooth muscle growth, and enteric neuron patterning, while the Ret signaling pathway is selectively required for enteric neuron migration, proliferation, and differentiation. The growth arrest specific gene 1 (Gas1) encodes a GPI-anchored membrane protein known to bind to Sonic Hh (Shh), Indian Hh (Ihh), and Ret. However, its role in the GI tract has not been examined. Here we show that the Gas1 mutant GI tract, compared to the control, is shorter, has thinner smooth muscles, and contains more enteric progenitors that are abnormally distributed. These phenotypes are similar to those of the Shh mutant, supporting that Gas1 mediates most of the Shh activity in the GI tract. Because Gas1 has been shown to inhibit Ret signaling elicited by Glial cell line-derived neurotrophic factor (Gdnf), we explored whether Gas1 mutant enteric neurons displayed any alteration of Ret signaling levels. Indeed, isolated mutant enteric progenitors not only showed increased levels of phospho-Ret and its downstream effectors, phospho-Akt and phospho-Erk, but also displayed altered responses to Gdnf and Shh. We therefore conclude that phenotypes observed in the Gas1 mutant are due to a combination of reduced Hh signaling and increased Ret signaling.
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影响因子：
2.7
作者：
Chalazonitis, A;Rothman, TP;Gershon, MD
通讯作者：
Gershon, MD
DOI：
10.1083/jcb.200401077
发表时间：
2004-08-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fu M;Lui VC;Sham MH;Pachnis V;Tam PK
通讯作者：
Tam PK
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：
11.8
作者：
Allen, Benjamin L.;Song, Jane Y.;Izzi, Luisa;Althaus, Irene W.;Kang, Jong-Sun;Charron, Frederic;Krauss, Robert S.;McMahon, Andrew P.
通讯作者：
McMahon, Andrew P.
影响因子：
10.5
作者：
Jain, S;Encinas, M;Milbrandt, J
通讯作者：
Milbrandt, J