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

描述（由申请人提供）：在黑腹果蝇中，成体生殖系的祖细胞，即原始生殖细胞（PGC），形成于前细胞胚盘胚胎的后极。原始生殖细胞的特化和发育过程与周围的索马有很大的不同。其中的差异是早熟细胞化，隔离外表面的胚胎，有限的有丝分裂潜力，转录静止和特殊的染色质结构。与索马不同的是，PGC身份的特化和随后的阐述被认为完全依赖于细胞自主因子，这些因子在卵子发生期间在卵母细胞的后部组装成专门的细胞质，即极质。除了协调PGC的发展，这些母体因素被认为是隔离新形成的PGC的细胞-细胞信号传导途径的不利影响，部署到模式相邻的索马。然而，我们对BMP信号通路的初步实验挑战了这种长期持有的PGC特异性的观点。我们发现，PGCs不仅能够响应来自索马的BMP信号，而且这些信号影响PGCs的规格和发展。在本申请中概述的研究中，我们建议重新检查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如何随后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中期胚胎发生期间合并成胚胎性腺之间的时期中在发育中的PGC中起什么作用。在胚胎发育中期，我们的研究将集中在这一途径如何影响PGCs转化为GCS。我们还将分析BMP途径在PGCs/GSC女性化中的意外和新作用。在早期胚胎中，我们的研究将集中在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源性因子交叉，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特定的基因活性模式中起着重要作用。

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.