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In most organisms, germ cells are formed distant from the somatic part of the gonad and thus have to migrate along and through a variety of tissues to reach the gonad. Transepithelial migration through the posterior midgut (PMG) is the first active step during Drosophila germ cell migration. Here we report the identification of a novel G protein-coupled receptor (GPCR), Tre1, that is essential for this migration step. Maternal tre1 RNA is localized to germ cells, and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos, most germ cells do not exit the PMG. The few germ cells that do leave the midgut early migrate normally to the gonad, suggesting that this gene is specifically required for transepithelial migration and that mutant germ cells are still able to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration, suggesting that Tre1 signals through Rho1. We propose that Tre1 acts in a manner similar to chemokine receptors required during transepithelial migration of leukocytes, implying an evolutionarily conserved mechanism of transepithelial migration. Recently, the chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells. Thus, germ cells may more generally use GPCR signaling to navigate the embryo toward their target.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.01.042 Byline: Andrew D. Renault, Sara Ricardo, Prabhat S. Kunwar, Ana Santos, Michelle Starz-Gaiano, Jennifer A. Stein, Ruth Lehmann Keywords: Primordial germ cells; Drosophila; Hedgehog; HMGCoA reductase; tout velu Abstract: In many species, the germ cells, precursors of sperm and egg, migrate during embryogenesis. The signals that regulate this migration are thus essential for fertility. In flies, lipid signals have been shown to affect germ cell guidance. In particular, the synthesis of geranylgeranyl pyrophosphate through the 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (Hmgcr) pathway is critical for attracting germ cells to their target tissue. In a genetic analysis of signaling pathways known to affect cell migration of other migratory cells, we failed to find a role for the Hedgehog (Hh) pathway in germ cell migration. However, previous reports had implicated Hh as a germ cell attractant in flies and suggested that Hh signaling is enhanced through the action of the Hmgcr pathway. We therefore repeated several critical experiments and carried out further experiments to test specifically whether Hh is a germ cell attractant in flies. In contrast to previously reported findings and consistent with findings in zebrafish our data do not support the notion that Hh has a direct role in the guidance of migrating germ cells in flies. Author Affiliation: HHMI and Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Cell Biology, New York University School of Medicine, New York, NY, 10016, USA Article History: Received 14 November 2008; Revised 28 January 2009; Accepted 28 January 2009

Many aspects of germ line development are conserved among animal species. In most species, primordial germ cells (PGCs) are set aside early in development of the embryo and in species as diverse as Xenopus, Drosophila and C. elegans, PGCs form in a specialized cytoplasm, the germ plasm, which is synthesized during oogenesis. Germ cells generally arise at a position in the embryo separate from that of the primordium of the somatic gonad and migrate through different tissue to reach the somatic gonad. Eventually germ cells undergo meiosis and differentiate into either egg or sperm. Although many genes have been identified in various species that affect the development of germ cells, we understand little about what determines the germ cell's unique fate. Some genes such as vasa, nanos and DAZ/boule are specifically expressed in germ cells of many species including C elegans, Drosophila, zebrafish, Xenopus and mouse. However, the role these genes play in germ cell development may vary in different organisms. We will report on a series of extensive genetic screens to identify genes that affect germ cell formation and migration in Drosophila and will compare the conclusions derived from these studies to those obtained in other systems.

Diffusible signals provide critical information to cells in biological systems, often in a concentration-dependent manner. In animal development, such signals can determine different cell fates or guide motile cells to their proper locations. It is well-known that migrating cells respond to graded chemoattractant cues by moving toward areas of higher concentrations. However, it is not clear how cell-dense animal tissues impact the distribution of chemoattractants in three dimensions. We leverage the simple architecture of the Drosophila egg chamber to explore this idea. In this context, sixteen large germline cells are packed together, enveloped by a somatic epithelium. A small set of epithelial cells, the border cells, form a motile cell cluster and respond to guidance signals by moving across the egg chamber during oogenesis. We created a geometrically-realistic model of the egg chamber and determined the distribution of the chemoattractants through that domain using a reaction-diffusion system. We used this information to determine reasonable biophysical parameters of chemoattractant that would facilitate gradient formation in the appropriate developmental time, and to explore the effects of different secretion locations in the egg chamber. Our model revealed several interesting features: The chemoattractant is more concentrated and the gradient sets up more quickly in a cell-packed space, and cell packing creates dips in the concentration and changes in gradient along the migratory path. We simulated migration with our calculated chemoattractant gradient and compared it to that with a constant gradient. We found that with our calculated gradient, migration was slower initially than in the constant gradient, which could be due to the exponential nature of the gradient or other variation in signal due to the heterogeneous domain. Given the many situations in which cell migration occurs in complex spatio-temporal environments, including development, immune response, and cancer metastasis, we believe modeling chemoattractant distribution in heterogeneous domains is widely relevant. [ABSTRACT FROM AUTHOR]

In most organisms, germ cells are formed distant from the somatic part of the gonad and thus have to migrate along and through a variety of tissues to reach the gonad. Transepithelial migration through the posterior midgut (PMG)is the first active step during Drosophila germ cell migration. Here we report the identification of a novel G protein-coupled receptor (GPCR), Tre1, that is essential for this migration step. Maternal tre1 RNA is localized to germ cells,and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos, most germ cells do not exit the PMG. The few germ cells that do leave the midgut early migrate normally to the gonad, suggesting that this gene is specifically required for transepithelial migration and that mutant germ cells are still able to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration,suggesting that Tre1 signals through Rho1. We propose that Tre1 acts in a manner similar to chemokine receptors required during transepithelial migration of leukocytes, implying an evolutionarily conserved mechanism of transepithelial migration. Recently,the chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells. Thus, germ cells may more generally use GPCR signaling to navigate the embryo toward their target. [ABSTRACT FROM AUTHOR]

Lipids, in addition to being structural components of cell membranes, can act as signaling molecules. Bioactive lipids, such as sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA), may act intracellularly as second messengers or be secreted and act as intercellular signaling molecules. Such molecules can affect a variety of cellular processes including apoptosis, proliferation, differentiation and motility. To investigate possible sources of bioactive lipids during development we have searched the Drosophila genome for homologs of genes involved in mammalian S1P and LPA metabolism. Here we report the developmental expression of 31 such genes by in situ hybridization to Drosophila embryos. Most show expression in specific tissues, with expression in the gut and nervous system being recurring patterns. [Copyright &y& Elsevier]