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

摘要 在果蝇中，形成了成年生殖系的祖先，原始生殖细胞(PGCs) 在细胞前胚泡胚胎的后极。Pgcs规范的制定过程和 发展与周围的索马有很大的不同。不同之处在于早熟 细胞化，胚胎外表面隔离，有丝分裂潜能受限，转录 宁静和特殊的染色质结构。与SOMA不同的是，该规范和后续 PGC特性的阐述被认为完全依赖于组装的细胞自主因子 在卵子发生的过程中，在卵母细胞的后部变成一种特殊的细胞质，即极质。除了……之外 这些母性因素协调着PGC的发展，被认为是将新形成的PGC与 细胞-细胞信号通路的不利影响，这些信号通路被用来形成邻近的胞体。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，PGCs不仅能够对来自胞体的BMP信号做出反应，而且这些信号 信号影响着PGC的规范和发展。在本申请中概述的研究中，我们 建议重新审视PGC规范的问题，侧重于这种非自治的作用 PGC发育中的信号通路。我们将调查几个对我们的 对PGC命运如何决定以及PGC随后如何决定的机制的理解 发育成生殖系干细胞(GSCs)。我们将确定BMP信号通路所起的作用 在早期胚胎中从这些细胞的形成到它们的 在胚胎发育中期融合成胚胎性腺。在胚胎发育中期，我们的研究将 重点关注这一途径如何影响PGCs向GCS的转变。我们还将分析一个意想不到的 BMP途径在PGCs/GSCs女性化中的新作用。在早期胚胎中，我们的研究将 重点介绍规范和维护PGC身份所涉及的机制。我们会调查的 BMP途径如何与细胞自主母体因子相交建立和阐述PGC 命运。我们还将确定BMP途径是否在编程PGC中发挥重要作用 基因活动的特定模式。

ABSTRACT 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.