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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.