Molecular mechanisms of cell fate specification

基因调控网络指导神经源性动物板域（APD）的规范（55%）。 使用生物信息学以及基于微阵列和原位杂交筛选，我们已经确定了大多数的调节蛋白（50）在动物板中选择性表达。 我们将通过监测单个基因功能丧失对其他基因表达的定量水平和空间模式的影响来确定基因的位置。 最有趣的基因之一是FoxQ 2，它是已知最早的APD特异性基因，我们今年发现它是APD中三种已知细胞类型分化所必需的。 出乎意料的是，FoxQ 2还抑制了nodal的表达，nodal编码的关键信号分子启动了胚胎次级轴沿着的图案化。FoxQ 2通过依赖于来自底层植物卵裂球的典型Wnt信号的信号从结节反应动物半球中消除。我们认为FoxQ 2提供了一个连接Wnt和nodal信号的检查点，它协调胚胎主轴和次级轴的发育。这是一种新的机制，对于建立胚胎的主要组织类型至关重要，并且已经提交了手稿以供出版（Yaguchi，S.，Yaguchi，J.，安格雷尔河和Angerer，L.M.（2007）Wnt-FoxQ2-nodal pathway links primary and secondary axis specification in sea urchin embryos. Dev. Cell，in review.） 早期内胚层特化的机制。(25%) 我们已经发现，通过Alk 4/5/7受体的激活素B信号传导是在卵裂阶段期间从微粒体及其后代发送的经典信号，这是内胚层发育和适时原肠胚形成所需的。这种早期信号被认为是海胆胚胎内胚层发育中的第一个核b-连环蛋白依赖步骤。 激活素B或Alk 4/5/7功能的丧失模拟微粒的丧失，并且异位激活素B信号传导可以由异位微粒诱导。 我们已经鉴定了内胚层基因调控网络中响应激活素B信号传导的特定基因子集。 由于这些结果改变了海胆内中胚层基因调控网络的现状，主要目标是确定激活素B信号传导如何适应内胚层特化的机制。 一份手稿是在塞西，A.，安格雷尔河和Angerer，L.M.（2007）ActivinB/Alk4/5/7 signaling is an early micromere-dependent signal required for early endoderm specification in sea urchin embryos）。 生物信息学。(20%) 我们通过将所有海胆基因预测与GO类别、时间表达和转录组数据联系起来，继续改进公开可用的海胆基因序列分析计算方法。 这些方法对于构建控制不同细胞类型发育的基因的综合网络至关重要。

The gene regulatory network guiding specification of the neurogenic animal plate domain (APD)(55%). Using bioinformatics as well as microarray-based and in situ hybridization screens, we have identified most of the regulatory proteins (50) expressed selectively in the animal plate. We will determine positions of genes with the network by monitoring effects of loss of individual gene functions on quantitative levels and spatial patterns of expression of the others. One of the most interesting genes is FoxQ2, the earliest known APD-specific gene, which we showed this year to be necessary for differentiation of the three known cell types in the APD. Unexpectedly, FoxQ2 also inhibits expression of nodal, which encodes the key signaling molecule that initiates patterning along the secondary axis of the embryo. FoxQ2 is eliminated from the nodal-responsive animal hemisphere by signals dependent on canonical Wnt signaling from underlying vegetal blastomeres. We propose that FoxQ2 provides a checkpoint linking Wnt and nodal signals, which coordinates development long the primary and secondary axes of the embryo. This is a new mechanism that is critical for establishing the major tissue types of the embryo and a manuscript has been submitted for publicatin (Yaguchi, S., Yaguchi, J., Angerer, R.C. and Angerer, L.M. (2007) A Wnt-FoxQ2-nodal pathway links primary and secondary axis specification in sea urchin embryos. Dev. Cell, in review.) The mechanisms of early endoderm specification.(25%) We have discovered that ActivinB signaling through the Alk4/5/7 receptor is the classic signal sent during cleavage stages from micromeres and their progeny, which is required for endoderm development and timely gastrulation. This early signal is thought to be the first nuclear b-catenin-dependent step in sea urchin embryo endoderm development. Loss of either ActivinB or Alk4/5/7 function mimics loss of micromeres and ectopic ActivinB signaling can be induced by ectopic micromeres. We have identified a specific subset of genes in the endoderm gene regulatory network that respond to ActivinB signaling. Because these results alter the current status of the sea urchin endomesoderm gene regulatory network, a major goal is to determine how ActivinB signaling fits into the mechanism underlying endoderm specification. A manuscript is in preparatino (Sethi, A., Angerer, R.C. and Angerer, L.M. (2007) ActivinB/Alk4/5/7 signaling is an early micromere-dependent signal required for early endoderm specification in sea urchin embryos). Bioinformatics.(20%) We continued to improve publicly available computational methods for sequence analysis of sea urchin genes by linking all of the sea urchin gene predictions to GO categories, to temporal expression and transcriptome data. These methods are essential for building the comprehensive networks of genes that control development of different cell types.