SMAD AND FAST-1 SIGNALS IN EARLY XENOPUS DEVELOPMENT

描述(逐字摘自调查员摘要)： TGFb超家族生长因子在骨髓瘤的形成中发挥核心作用 脊椎动物早期胚胎的轴型。我们已经使用了非洲爪哇的胚胎 作为鉴定新的母系转录因子FAST-1的模型系统， 这是中轴胚层基因规范的关键调节因子。 TGFb配体在早期胚胎发育过程中的程序。我们还建立了 FAST-1由与Smads的直接相互作用调节，Smads是最近的一种 确定了TGFb信号换能器的类别。我们现在将检查：1)-1)有多快 有助于早期胚胎基因表达的图案化2)1有多快 以及3)Smad的内生时空模式是如何 激活在胚胎中受到调节。表达式需要FAST-1 各种各样的早期中胚层基因，但我们不了解 FAST-1在转录调控中的作用 内源基因表达。我们将使用FAST-1调控的转基因分析 基因组记者将研究FAST-1在细胞周期调控中的作用 中胚层基因表达对内源性反应的复杂模式 诱导信号。正确的发展模式同样取决于 胚胎细胞对特定信号的反应能力，就像它在 正确定位信号本身。我们已经确定了几种方法 胚胎细胞对诱导信号的反应能力是 受监管的。一种涉及对FAST-Smad复合体的调节 原肠形成，第二个涉及启动子特异性的反应性调节 在原肠形成结束后，为了快速激活，第三个过程涉及相互作用 原肠前期胚胎中成纤维细胞生长因子和成纤维细胞生长因子b信号之间的关系。我们计划确定 这些不同的能力监管机制的机制基础 阐明单个细胞间信号如何 随着胚胎发育的进展，调节不同的发育事件。虽然 我们知道Smad对早期胚胎模式很重要，但我们不知道 这些监管机构在何时何地积极参与早期开发。我们有 发展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。关于监管的调查研究 内源性Smad活性将使我们能够批判性地测试各种 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.