Unexpected roles for BMP signaling in the specification of the embryonic germline

BMP 信号在胚胎种系规范中的意外作用

• 批准号: 8837033
• 负责人: Paul D Schedl
• 金额: $ 30.34万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-11 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8837033
• 关键词: Address; Adult; Adverse effects; Animal Model; Animals; Architecture; Blastoderm; Cell Cycle; Cells; Characteristics; Chromatin; Cues; Cytoplasm; Deposition; Development; Drosophila genus; Drosophila melanogaster; Embryo; Embryonic Development; Female; Feminization; Generations; Genes; Germ Cells; Gonadal structure; Health; Maintenance; Messenger RNA; Mitotic; Oocytes; Oogenesis; Organism; Pathway interactions; Pattern; Play; Process; Proteins; RNA Interference; Research; Role; Signal Pathway; Signal Transduction; Somatic Cell; Specific qualifier value; Staging; Stem cells; Structure of primordial sex cell; Surface; Tissues; Transplantation; base; cell type; germline stem cells; intercellular communication; neuronal cell body; novel; progenitor; programs; research study; stem cell fate; transcription factor; translation factor

DESCRIPTION (provided by applicant): In Drosophila melanogaster the progenitors of the adult germline, the primordial germ cells (PGCs), are formed at the posterior pole of the pre-cellular blastoderm embryo. The process of PGCs specification and development differs substantially from that of the surrounding soma. Amongst the differences are precocious cellularization, sequestration on the outside surface of the embryo, limited mitotic potential, transcriptional quiescence and a special chromatin architecture. Also unlike the soma, the specification and subsequent elaboration of PGC identity is thought to depend exclusively on cell autonomous factors that are assembled into a specialized cytoplasm, the pole plasm, at the posterior of the oocyte during oogenesis. In addition to orchestrating PGC development, these maternal factors are thought to insulate newly formed PGCs from the adverse effects of the cell-cell signaling pathways that are deployed to pattern the neighboring soma. However, our preliminary experiments on the BMP signaling pathway challenge this long held view of PGC specification. We find that PGCs are not only capable of responding to BMP signals from the soma, but also that these signals impact the specification and development of the PGCs. In the studies outlined in this application we propose to re-examine the problem of PGC specification, focusing on the role of this non-autonomous signaling pathway in PGC development. We will investigate several issues that are central to our understanding of the mechanisms underlying how PGC fate is determined and how the PGCs subsequently development into germline stem cells (GSCs). We will determine what role the BMP signaling pathway plays in the developing PGCs in the period between the formation of these cells in the early embryo and their coalescence into the embryonic gonad during mid-embryogenesis. In mid-embryogenesis, our studies will focus on how this pathway impacts the transformation of PGCs into GCSs. We will also analyze an unexpected and novel role of the BMP pathway in the feminization of the PGCs/GSCs. In the early embryo, our studies will focus on the mechanisms involved in the specification and maintenance of PGC identity. We will investigate how the BMP pathway intersects with the cell autonomous maternal factors to establish and elaborate PGC fate. We will also determine whether the BMP pathway plays an instrumental role in programming PGC specific patterns of gene activity.

描述（由申请人提供）：在果蝇中，成体种系的祖细胞，即原始生殖细胞（PGC），在前细胞胚盘胚胎的后极形成。 PGC 的规范和发育过程与周围的体细胞有很大不同。其中的差异包括早熟的细胞化、胚胎外表面的隔离、有限的有丝分裂潜力、转录静止和特殊的染色质结构。与胞体不同的是，PGC 身份的规范和随后的阐述被认为完全取决于细胞自主因子，这些细胞自主因子在卵子发生过程中在卵母细胞后部组装成特殊的细胞质，即极质。除了协调 PGC 的发育外，这些母体因素还被认为可以使新形成的 PGC 免受细胞间信号传导途径的不利影响，这些信号传导途径用于模拟邻近的体细胞。然而，我们对 BMP 信号通路的初步实验挑战了长期以来对 PGC 规范的看法。我们发现 PGC 不仅能够响应来自体细胞的 BMP 信号，而且这些信号也会影响 PGC 的规格和发育。在本申请概述的研究中，我们建议重新审视 PGC 规范的问题，重点关注这种非自主信号通路在 PGC 发展中的作用。我们将研究几个问题，这些问题对于我们理解 PGC 命运如何决定以及 PGC 随后如何发育成生殖系干细胞 (GSC) 的机制至关重要。我们将确定 BMP 信号通路在早期胚胎中这些细胞的形成和胚胎发生中期合并成胚胎性腺之间的时期在发育中的 PGC 中发挥什么作用。在胚胎发生中期，我们的研究将集中于该途径如何影响 PGC 向 GCS 的转化。我们还将分析 BMP 通路在 PGC/GSC 女性化中的意想不到的新颖作用。在早期胚胎中，我们的研究将重点关注 PGC 身份的规范和维护所涉及的机制。我们将研究 BMP 通路如何与细胞自主母体因素相交叉，以建立和阐述 PGC 的命运。我们还将确定 BMP 通路是否在编程 PGC 特定基因活动模式中发挥重要作用。