SMAD AND FAST-1 SIGNALS IN EARLY XENOPUS DEVELOPMENT

描述（根据研究者摘要逐字附上）： TGFB生长因子超家族在建立人胚肺成纤维细胞中起着重要作用。 早期脊椎动物胚胎的轴向模式。我们用非洲爪蟾胚胎 作为一个模型系统来鉴定一种新的母体转录因子，FAST-1， 它是轴向中胚层基因特化的关键调节因子 在早期胚胎发生过程中通过TGFB配体编程。我们还建立 FAST-1是通过与Smads的直接相互作用来调节的，最近， 识别类TGFB信号传感器。我们现在将研究：1）FAST-1 有助于早期胚胎基因表达的模式2）FAST-1是如何 调节，以及3）如何内源性的空间和时间模式的Smad 激活在胚胎中受到调节。FAST-1是表达式所必需的 各种各样的早期中胚层基因，但我们不明白， FAST-1转录调节对特定模式的贡献 内源基因表达我们将使用FAST-1调节的转基因分析， 研究FAST-1在调节 中胚层基因表达的复杂模式， 诱导信号。正确的发育模式同样取决于 胚胎细胞对特定信号作出反应的能力，就像在 信号本身的正确定位。我们已经确定了几种方法 其中胚胎细胞响应诱导信号的能力被 监管.一个涉及FAST-Smad复合物的调节， 第二个涉及启动子特异性的反应调节 在原肠胚形成结束后激活FAST-1，第三个涉及相互作用 FGF和TGFB信号之间的关系。我们计划确定 这些不同的能力调节机制的机械基础， 阐明了单个细胞间信号如何 在胚胎发生过程中调节不同的发育事件。虽然 我们知道Smads对早期胚胎形成很重要，但我们不知道 这些监管机构在早期发展中的活跃时间和地点。我们有 开发了一种新的方法来研究内源性激活状态， 适用于早期胚胎的Smads。调查管制 内源性Smad活性将使我们能够严格测试各种 关于TGFBs在早期发育中作用的假说。

DESCRIPTION (appended verbatim from investigator's abstract): Members of the TGFB superfamily of growth factors play a central role in the establishment of axial pattern in the early vertebrate embryo. We have used the Xenopus embryo as a model system to identify a novel maternal transcription factor, FAST-1, that is a key regulator of the specification of the axial mesodermal gene program by TGFB ligands during early embryogenesis. We have also established that FAST-1 is regulated by direct interaction with Smads, a recently identified class of TGFB signal transducers. We will now examine: 1) how FAST-1 contributes to patterning of early embryonic gene expression 2) how FAST-1 is regulated, and 3) how the endogenous spatial and temporal patterns of Smad activation are regulated in the embryo. FAST-1 is necessary for the expression of a wide variety of early mesodermal genes, but we do not understand the contribution of transcriptional regulation by FAST-1 to specific patterns of endogenous gene expression. We will use transgenic analysis of FAST-1 regulated genomic reporters to investigate the role of FAST-1 in the regulation of complex patterns of mesodermal gene expression in response to endogenous inducing signals. Correct developmental patterning depends as much on the competence of embryonic cells to respond to specific signals as it does on the correct localization of the signals themselves. We have identified several ways in which the competence of embryonic cells to respond to inducing signals is regulated. One involves the regulation of FAST-Smad complexes at the start of gastrulation, a second involves promoter-specific regulation of responsiveness to activated FAST-1 after the end of gastrulation, a third involves interaction between FGF and TGFB signals in the pre-gastrula embryo. We plan to determine the mechanistic basis for these various mechanisms for competence regulation to clarify the fundamental problem of how single intercellular signals can regulate different developmental events as embryogenesis progresses. Although we know that Smads are important for early embryonic patterning, we do not know where and when these regulators are active in early development. We have developed a new approach to the study of the endogenous state of activation of Smads that is applicable to early embryos. Investigation of the regulation of endogenous Smad activity will allow us to critically test a variety of hypotheses concerning the role of TGFBs in early development.