Retinoic acid signaling regulates sonic hedgehog and bone morphogenetic protein signalings during genital tubercle development.
Retinoic acid signaling regulates sonic hedgehog and bone morphogenetic protein signalings during genital tubercle development.
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DOI：
10.1002/bdrb.20344
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发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Yamada G
中科院分区：
文献类型：
--
作者：
Liu L;Suzuki K;Nakagata N;Mihara K;Matsumaru D;Ogino Y;Yashiro K;Hamada H;Liu Z;Evans SM;Mendelsohn C;Yamada G
视黄酸（RA）在器官发生中起着关键作用，过量和减少量的RA都会导致发育异常。生殖器官易受致畸剂致畸作用的影响，生殖结节（GT）就是这样一个代表性器官。在GT的发展过程中，内源性RA信号的生理功能和RA诱导致畸的机制知之甚少。本研究的目的是通过分析转基因小鼠模型来了解RA在GT发展过程中的发育和致畸作用。我们发现了动态模式的基因表达的RA合成酶，Raldh 2，和RA分解代谢酶，Cyp 26 b1，GT的发展过程中。RA信号的指示基因Rarb在阴茎海绵体和尿道板上皮（UE）中开始表达，在GT发育过程中起着重要作用。Cyp 26 b1 −/−突变体中过量的RA信号传导导致GT发育期间细胞增殖和分化的异常程度，并且还上调生长因子信号传导的表达。它们包括Sonic hedgehog（Shh）信号传导和骨形态发生蛋白（Bmp）信号传导，其在UE及其双侧间充质中表达。RA信号正调控GT发展过程中的sShh和Bmp 4的表达也证明了RA管理和RA信号突变体的功能丧失的分析实验。因此，RA信号转导参与UE形成和GT发育所必需的发育级联。
Retinoic acid (RA) plays pivotal roles in organogenesis, and both excessive and reduced amounts of RA cause developmental abnormalities. Reproductive organs are susceptible to teratogen toxigenicity, and the genital tubercle (GT) is one such representative organ. The physiological function of endogenous RA signaling and the mechanisms of RA-induced teratogenicity are poorly understood during the GT development. The objective of this study is to understand the developmental and teratogenic roles of RA during GT development by analyzing genetically modified mouse models. We found dynamic patterns of gene expression for the RA-synthesizing enzyme, Raldh2, and for the RA-catabolizing enzyme, Cyp26b1, during GT development. Rarb, an indicator gene for RA signaling, starts its expression in the prospective corpus cavernosum penis and in the urethral plate epithelium (UE), which plays central roles during GT development. Excessive RA signaling in Cyp26b1−/− mutants leads to abnormal extents of cell proliferation and differentiation during GT development, and also upregulates expression of growth factor signalings. They include Sonic hedgehog (Shh) signaling and Bone morphogenetic protein (Bmp) signaling, which are expressed in the UE and its bilateral mesenchyme. RA signaling positively regulatesShh and Bmp4 expression during GT development as testified also by the experiment of RA administration and analyses of loss–of-function of RA signaling mutants. Thus, RA signaling is involved in the developmental cascade necessary for UE formation and GT development.
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影响因子：
64.5
作者：
Duester G
通讯作者：
Duester G
影响因子：
10.5
作者：
Abu-Abed, S;Dollé, P;Petkovich, M
通讯作者：
Petkovich, M
DOI：
10.1006/bbrc.1997.7124
发表时间：
1997-08-28
影响因子：
3.1
作者：
Feil, R;Wagner, J;Chambon, P
通讯作者：
Chambon, P
影响因子：
2.5
作者：
HARNISH, DC;JIANG, H;SOPRANO, DR
通讯作者：
SOPRANO, DR
影响因子：
3.7
作者：
Pask, Andrew J.;McInnes, Kerry J.;Short, Roger V.
通讯作者：
Short, Roger V.