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Tre1, a G protein-coupled receptor, directs transepithelial migration of Drosophila germ cells.

Kunwar PS, Starz-Gaiano M, Bainton RJ, Heberlein U, Lehmann R - PLoS Biol. (2003)

Bottom Line: In tre1 mutant embryos, most germ cells do not exit the PMG.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.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Developmental Genetics Program, New York University School of Medicine, New York, New York, USA.

ABSTRACT
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.

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Related in: MedlinePlus

A Summary of Early Germ Cell Migration Steps and Genes(A) For each stage, the position of germ cells (yellow) and midgut (red) is indicated. Yellow arrows point in the direction of migration. Note that in wild-type embryos, few germ cells can be observed on the basal side of the midgut anlage (black arrow, stage 7). Genes known for their specific role in germ cell guidance are indicated next to the step where the activity of the respective gene product is needed. In addition to the genes listed, a role for hedgehog has been suggested in germ cell migration (Desphpande et al. 2001); however, the exact step affected is unclear.(B–G) Overexpression of EP1631 in germ cells and expression pattern of CG4322. Anterior is to the left in all panels. (B), (C), (F), and (G) are lateral views; (D) and (E) are top views. Wild-type embryos (B and D) and embryos overexpressing EP1631 (CG4322 GPCR) in germ cells (C and E) were stained with anti-Vasa to mark germ cells. At stage 11 (B and C), germ cells in the wild-type (B) associate with the mesoderm, while germ cells expressing EP1631 (CG4322 GPCR) using the germ cell-specific nos-GAL4 driver are disorganized (C). When the gonads are normally coalescing at stage 13 in wild-type control embryos (D), many germ cells expressing the CG4322 GPCR remain lost and are found in ectopic locations (E; arrow points to few germ cells in gonad). (F and G) Expression pattern of CG4322 RNA. CG4322 RNA is detected in hemocytes (asterisk), in the caudal visceral mesoderm (arrow), and in the PMG at stage 9 (F) and in midgut (arrow) and glial cells (arrowhead) at stage 13 (G).
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pbio.0000080-g001: A Summary of Early Germ Cell Migration Steps and Genes(A) For each stage, the position of germ cells (yellow) and midgut (red) is indicated. Yellow arrows point in the direction of migration. Note that in wild-type embryos, few germ cells can be observed on the basal side of the midgut anlage (black arrow, stage 7). Genes known for their specific role in germ cell guidance are indicated next to the step where the activity of the respective gene product is needed. In addition to the genes listed, a role for hedgehog has been suggested in germ cell migration (Desphpande et al. 2001); however, the exact step affected is unclear.(B–G) Overexpression of EP1631 in germ cells and expression pattern of CG4322. Anterior is to the left in all panels. (B), (C), (F), and (G) are lateral views; (D) and (E) are top views. Wild-type embryos (B and D) and embryos overexpressing EP1631 (CG4322 GPCR) in germ cells (C and E) were stained with anti-Vasa to mark germ cells. At stage 11 (B and C), germ cells in the wild-type (B) associate with the mesoderm, while germ cells expressing EP1631 (CG4322 GPCR) using the germ cell-specific nos-GAL4 driver are disorganized (C). When the gonads are normally coalescing at stage 13 in wild-type control embryos (D), many germ cells expressing the CG4322 GPCR remain lost and are found in ectopic locations (E; arrow points to few germ cells in gonad). (F and G) Expression pattern of CG4322 RNA. CG4322 RNA is detected in hemocytes (asterisk), in the caudal visceral mesoderm (arrow), and in the PMG at stage 9 (F) and in midgut (arrow) and glial cells (arrowhead) at stage 13 (G).

Mentions: Several studies in Drosophila have identified genes that specifically affect separate steps in the germ cell migration and gonad formation processes (Warrior 1994; Williamson and Lehmann 1996; Moore et al. 1998a; Starz-Gaiano and Lehmann 2001). Primordial germ cells are formed at the posterior pole underlying somatic cells that give rise to the posterior midgut (PMG) anlage. During gastrulation, germ cells adhering to the PMG anlage are carried inside the embryo (for a summary of early migration events, see Figure 1A). From the blind end of the PMG primordium, germ cells start an active journey by transmigrating through midgut epithelium, moving from its apical to its basal side (Callaini et al. 1995; Jaglarz and Howard 1995). Once germ cells pass through the PMG, they migrate along the midgut toward the nearby mesoderm. From there, they transit from the midgut to the mesoderm, where they associate with three lateral clusters of gonadal mesoderm cells (somatic gonadal precursors [SGPs]). Germ cells adhere tightly to these clusters as they merge and coalesce into a gonad (Brookman et al. 1992; Moore et al. 1998b; Van Doren et al. 2003). Attractant and repellent germ cell guidance factors have been identified in genetic screens. During their migration on the midgut, germ cells move away from Wunen-expressing cells (Zhang et al. 1996, 1997; Starz-Gaiano et al. 2001). The two wunen genes encode homologs of lipid phosphate phosphatase 3 (LPP3) and are believed to catalyze phosopholipid dephosphorylation (Zhang et al. 1997; Starz-Gaiano et al. 2001; Burnett and Howard 2003). It has been suggested that Wunen proteins act to produce a repellent signal or to destroy a phospholipid acting as an attractant. In the mesoderm, germ cells are attracted by gonadal mesodermal cells that express 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) and Hedgehog (Van Doren et al. 1998a; Deshpande et al. 2001).


Tre1, a G protein-coupled receptor, directs transepithelial migration of Drosophila germ cells.

Kunwar PS, Starz-Gaiano M, Bainton RJ, Heberlein U, Lehmann R - PLoS Biol. (2003)

A Summary of Early Germ Cell Migration Steps and Genes(A) For each stage, the position of germ cells (yellow) and midgut (red) is indicated. Yellow arrows point in the direction of migration. Note that in wild-type embryos, few germ cells can be observed on the basal side of the midgut anlage (black arrow, stage 7). Genes known for their specific role in germ cell guidance are indicated next to the step where the activity of the respective gene product is needed. In addition to the genes listed, a role for hedgehog has been suggested in germ cell migration (Desphpande et al. 2001); however, the exact step affected is unclear.(B–G) Overexpression of EP1631 in germ cells and expression pattern of CG4322. Anterior is to the left in all panels. (B), (C), (F), and (G) are lateral views; (D) and (E) are top views. Wild-type embryos (B and D) and embryos overexpressing EP1631 (CG4322 GPCR) in germ cells (C and E) were stained with anti-Vasa to mark germ cells. At stage 11 (B and C), germ cells in the wild-type (B) associate with the mesoderm, while germ cells expressing EP1631 (CG4322 GPCR) using the germ cell-specific nos-GAL4 driver are disorganized (C). When the gonads are normally coalescing at stage 13 in wild-type control embryos (D), many germ cells expressing the CG4322 GPCR remain lost and are found in ectopic locations (E; arrow points to few germ cells in gonad). (F and G) Expression pattern of CG4322 RNA. CG4322 RNA is detected in hemocytes (asterisk), in the caudal visceral mesoderm (arrow), and in the PMG at stage 9 (F) and in midgut (arrow) and glial cells (arrowhead) at stage 13 (G).
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Related In: Results  -  Collection

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pbio.0000080-g001: A Summary of Early Germ Cell Migration Steps and Genes(A) For each stage, the position of germ cells (yellow) and midgut (red) is indicated. Yellow arrows point in the direction of migration. Note that in wild-type embryos, few germ cells can be observed on the basal side of the midgut anlage (black arrow, stage 7). Genes known for their specific role in germ cell guidance are indicated next to the step where the activity of the respective gene product is needed. In addition to the genes listed, a role for hedgehog has been suggested in germ cell migration (Desphpande et al. 2001); however, the exact step affected is unclear.(B–G) Overexpression of EP1631 in germ cells and expression pattern of CG4322. Anterior is to the left in all panels. (B), (C), (F), and (G) are lateral views; (D) and (E) are top views. Wild-type embryos (B and D) and embryos overexpressing EP1631 (CG4322 GPCR) in germ cells (C and E) were stained with anti-Vasa to mark germ cells. At stage 11 (B and C), germ cells in the wild-type (B) associate with the mesoderm, while germ cells expressing EP1631 (CG4322 GPCR) using the germ cell-specific nos-GAL4 driver are disorganized (C). When the gonads are normally coalescing at stage 13 in wild-type control embryos (D), many germ cells expressing the CG4322 GPCR remain lost and are found in ectopic locations (E; arrow points to few germ cells in gonad). (F and G) Expression pattern of CG4322 RNA. CG4322 RNA is detected in hemocytes (asterisk), in the caudal visceral mesoderm (arrow), and in the PMG at stage 9 (F) and in midgut (arrow) and glial cells (arrowhead) at stage 13 (G).
Mentions: Several studies in Drosophila have identified genes that specifically affect separate steps in the germ cell migration and gonad formation processes (Warrior 1994; Williamson and Lehmann 1996; Moore et al. 1998a; Starz-Gaiano and Lehmann 2001). Primordial germ cells are formed at the posterior pole underlying somatic cells that give rise to the posterior midgut (PMG) anlage. During gastrulation, germ cells adhering to the PMG anlage are carried inside the embryo (for a summary of early migration events, see Figure 1A). From the blind end of the PMG primordium, germ cells start an active journey by transmigrating through midgut epithelium, moving from its apical to its basal side (Callaini et al. 1995; Jaglarz and Howard 1995). Once germ cells pass through the PMG, they migrate along the midgut toward the nearby mesoderm. From there, they transit from the midgut to the mesoderm, where they associate with three lateral clusters of gonadal mesoderm cells (somatic gonadal precursors [SGPs]). Germ cells adhere tightly to these clusters as they merge and coalesce into a gonad (Brookman et al. 1992; Moore et al. 1998b; Van Doren et al. 2003). Attractant and repellent germ cell guidance factors have been identified in genetic screens. During their migration on the midgut, germ cells move away from Wunen-expressing cells (Zhang et al. 1996, 1997; Starz-Gaiano et al. 2001). The two wunen genes encode homologs of lipid phosphate phosphatase 3 (LPP3) and are believed to catalyze phosopholipid dephosphorylation (Zhang et al. 1997; Starz-Gaiano et al. 2001; Burnett and Howard 2003). It has been suggested that Wunen proteins act to produce a repellent signal or to destroy a phospholipid acting as an attractant. In the mesoderm, germ cells are attracted by gonadal mesodermal cells that express 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) and Hedgehog (Van Doren et al. 1998a; Deshpande et al. 2001).

Bottom Line: In tre1 mutant embryos, most germ cells do not exit the PMG.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.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Developmental Genetics Program, New York University School of Medicine, New York, New York, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus