Pitx1 regulates cement gland development in Xenopus laevis through activation of transcriptional targets and inhibition of BMP signaling.
Pitx1 regulates cement gland development in Xenopus laevis through activation of transcriptional targets and inhibition of BMP signaling.
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DOI：
10.1016/j.ydbio.2018.03.008
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发表时间：
2018-05-01
影响因子：
2.7
通讯作者：
Weinstein DC
中科院分区：
文献类型：
--
作者：
Jin Y;Weinstein DC
非洲爪蟾（Xenopus laevis）的水泥腺长期以来一直被用作研究胚胎发生过程中细胞信号和转录因子相互作用的模型。研究表明，骨形态发生蛋白（Bone Morphogenetic Protein， BMP）信号的中间水平对骨水泥腺的形成至关重要。此外，一些转录因子与水泥腺的发育有关。其中一种，含有同源结构域的蛋白Pitx1，可以产生异位水泥腺体的形成；然而，这一过程背后的机制仍然不清楚。我们在此首次报道了体内水泥腺形成对Pitx蛋白的需求：敲低pitx1和密切相关的pitx2c抑制内源性水泥腺的形成。Pitx1通过直接和间接机制转录激活水泥腺体分化基因，并作为转录激活因子抑制BMP信号传导。这种抑制作用是pitx基因表达所必需的，部分由pitx1依赖性卵泡抑素表达介导。完全抑制BMP信号传导抑制Pitx1诱导水泥腺体标志物此外，我们发现Pitx1与细胞内BMP信号转导器Smad1相互作用。我们提出了一个水泥腺形成的模型，其中Pitx1限制水泥腺原基内的局部BMP信号，并招募Smad1来激活直接下游靶点。
The cement gland in Xenopus laevis has long been used as a model to study the interplay of cell signaling and transcription factors during embryogenesis. It has been shown that an intermediate level of Bone Morphogenetic Protein (BMP) signaling is essential for cement gland formation. In addition, several transcription factors have been linked to cement gland development. One of these, the homeodomain-containing protein Pitx1, can generate ectopic cement gland formation; however, the mechanisms underlying this process remain obscure. We report here, for the first time, a requirement for Pitx proteins in cement gland formation, in vivo: knockdown of both pitx1 and the closely related pitx2c inhibit endogenous cement gland formation. Pitx1 transcriptionally activates cement gland differentiation genes through both direct and indirect mechanisms, and functions as a transcriptional activator to inhibit BMP signaling. This inhibition, required for the expression of pitx genes, is partially mediated by Pitx1-dependent follistatin expression. Complete suppression of BMP signaling inhibits induction of cement gland markers by Pitx1; furthermore, we find that Pitx1 physically interacts with Smad1, an intracellular transducer of BMP signaling. We propose a model of cement gland formation in which Pitx1 limits local BMP signaling within the cement gland primordium, and recruits Smad1 to activate direct downstream targets.
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影响因子：
64.5
作者：
HEMMATIBRIVANLOU, A;MELTON, DA
通讯作者：
MELTON, DA
DOI：
10.1073/pnas.95.16.9337
发表时间：
1998-08-04
影响因子：
11.1
作者：
Iemura, S;Yamamoto, TS;Ueno, N
通讯作者：
Ueno, N
影响因子：
4.6
作者：
Deglincerti, Alessia;Haremaki, Tomomi;Brivanlou, Ali H.
通讯作者：
Brivanlou, Ali H.
影响因子：
2.6
作者：
Coumailleau, P;Penrad-Mobayed, M;Angelier, N
通讯作者：
Angelier, N
影响因子：
4.6
作者：
Chung, Mei-I;Nascone-Yoder, Nanette M.;Wallingford, John B.
通讯作者：
Wallingford, John B.