SIX1 cooperates with RUNX1 and SMAD4 in cell fate commitment of Müllerian duct epithelium.
SIX1 cooperates with RUNX1 and SMAD4 in cell fate commitment of Müllerian duct epithelium.
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DOI：
10.1038/s41418-020-0579-z
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发表时间：
2020-12
影响因子：
12.4
通讯作者：
Kurita T
中科院分区：
文献类型：
--
作者：
Terakawa J;Serna VA;Nair DM;Sato S;Kawakami K;Radovick S;Maire P;Kurita T
在雌性哺乳动物生殖道发育过程中，当间充质细胞诱导Δ Np 63转录因子表达时，下苗勒管上皮细胞定向分化为阴道和宫颈的复层鳞状上皮。Δ Np 63表达的缺失导致腺病，这是阴道腺癌的假定前体。我们之前的基因工程小鼠模型研究已经确定，成纤维细胞生长因子（FGF）/丝裂原活化蛋白激酶（MAPK）、骨形态发生蛋白（BMP）/SMAD和激活素A/runt-related transcription factor 1（RUNX 1）信号通路是苗勒管上皮（MDE）中Δ Np 63表达的独立必需条件。在此，我们报告sine oculis homeobox homolog 1（SIX 1）作为间充质信号的下游转录因子在MDE中Δ Np 63位点的激活中起关键作用。在发育中的小鼠生殖道中，SIX 1的表达仅限于未来子宫颈和阴道内的MDE。SIX 1表达在SMAD 4缺失MDE中完全不存在，并且在RUNX 1缺失和FGFR 2缺失MDE中减少，表明SIX 1受阴道间充质因子：BMP 4、激活素A和FGF 7/10的控制。此外，Six 1、Runx 1和Smad 4基因剂量依赖性地激活阴道穹窿内MDE中Δ Np 63的表达。利用己烯雌酚（DES）相关的阴道腺病小鼠模型，我们发现DES通过抑制阴道穹窿的SIX 1和RUNX 1，通过上皮雌激素受体α（ESR 1）抑制MDE中Δ Np 63位点的激活。
During female mammal reproductive tract development, epithelial cells of the lower Müllerian duct are committed to become stratified squamous epithelium of the vagina and ectocervix, when the expression of ΔNp63 transcription factor is induced by mesenchymal cells. The absence of ΔNp63 expression leads to adenosis, the putative precursor of vaginal adenocarcinoma. Our previous studies with genetically engineered mouse models have established that fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK), bone morphogenetic protein (BMP)/SMAD, and activin A/runt-related transcription factor 1 (RUNX1) signaling pathways are independently required for ΔNp63 expression in Müllerian duct epithelium (MDE). Here, we report that sine oculis homeobox homolog 1 (SIX1) plays a critical role in the activation of ΔNp63 locus in MDE as a downstream transcription factor of mesenchymal signals. In the developing mouse reproductive tract, SIX1 expression was restricted to MDE within the future cervix and vagina. SIX1 expression was totally absent in SMAD4 null MDE and was reduced in RUNX1 null and FGFR2 null MDE, indicating that SIX1 is under the control of vaginal mesenchymal factors: BMP4, activin A and FGF7/10. Furthermore, Six1, Runx1, and Smad4 gene-dose-dependently activated ΔNp63 expression in MDE within the vaginal fornix. Using a mouse model of diethylstilbestrol (DES)-associated vaginal adenosis, we found DES action through epithelial estrogen receptor α (ESR1) inhibits activation of ΔNp63 locus in MDE by transcriptionally repressing SIX1 and RUNX1 in the vaginal fornix.
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Contra V3：一种识别物种跨物种的转录因子结合位点的工具，更新2017。
影响因子：
14.9
作者：
Kreft L;Soete A;Hulpiau P;Botzki A;Saeys Y;De Bleser P
通讯作者：
De Bleser P
影响因子：
158.5
作者：
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Troisi, Rebecca
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3.6
作者：
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通讯作者：
Cunha, GR
DOI：
10.1016/0002-9378(72)90456-5
发表时间：
1972-01-01
影响因子：
9.8
作者：
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通讯作者：
FORSBERG, JG
影响因子：
2.9
作者：
Cunha, Gerald R.;Kurita, Takeshi;Baskin, Laurence S.
通讯作者：
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