Identification of genes controlling germ cell migration and embryonic gonad formation in Drosophila

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 667-678 ◽  
Author(s):  
L.A. Moore ◽  
H.T. Broihier ◽  
M. Van Doren ◽  
L.B. Lunsford ◽  
R. Lehmann
Keyword(s):  
Cell Migration ◽  
Germ Cell ◽  
Germ Cells ◽  
Cell Types ◽  
Drosophila Embryo ◽  
Specific Cell ◽  
Embryonic Patterning ◽  
Phenotypic Analysis ◽  
Embryonic Gonad ◽  
Germ Cell Migration

Gonadogenesis in the Drosophila embryo is a complex process involving numerous cellular migratory steps and cell-cell interactions. The mechanisms guiding germ cells to move through, recognize and adhere to specific cell types are poorly understood. In order to identify genes that are required for these processes, we have conducted an extensive mutagenesis of the third chromosome and screened for mutations disrupting germ cell migration at any point in embryonic development. Phenotypic analysis of these mutants demonstrates that germ cell migration can be broken down into discrete developmental steps, with each step requiring a specific set of genes. Many of these genes are involved in the development of gonadal mesoderm, the tissue that associates with germ cells to form the embryonic gonad. Moreover, mutations that we isolated affecting embryonic patterning as well as germ cell migration suggest that the origin of gonadal mesoderm lies within the eve domain of the developing mesoderm.

zfh-1 is required for germ cell migration and gonadal mesoderm development in Drosophila

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 655-666 ◽  
Author(s):  
H.T. Broihier ◽  
L.A. Moore ◽  
M. Van Doren ◽  
S. Newman ◽  
R. Lehmann
Keyword(s):  
Cell Migration ◽  
Germ Cell ◽  
Germ Cells ◽  
Ectopic Expression ◽  
Homeodomain Protein ◽  
Mesoderm Development ◽  
Visceral Mesoderm ◽  
Temporal Course ◽  
Germ Cell Migration

In Drosophila as well as many vertebrate systems, germ cells form extraembryonically and migrate into the embryo before navigating toward gonadal mesodermal cells. How the gonadal mesoderm attracts migratory germ cells is not understood in any system. We have taken a genetic approach to identify genes required for germ cell migration in Drosophila. Here we describe the role of zfh-1 in germ cell migration to the gonadal mesoderm. In zfh-1 mutant embryos, the initial association of germ cells and gonadal mesoderm is blocked. Loss of zfh-1 activity disrupts the development of two distinct mesodermal populations: the caudal visceral mesoderm and the gonadal mesoderm. We demonstrate that the caudal visceral mesoderm facilitates the migration of germ cells from the endoderm to the mesoderm. Zfh-1 is also expressed in the gonadal mesoderm throughout the development of this tissue. Ectopic expression of Zfh-1 is sufficient to induce additional gonadal mesodermal cells and to alter the temporal course of gene expression within these cells. Finally, through analysis of a tinman zfh-1 double mutant, we show that zfh-1 acts in conjunction with tinman, another homeodomain protein, in the specification of lateral mesodermal derivatives, including the gonadal mesoderm.

scholarly journals A Selective Screen Reveals Discrete Functional Domains in Drosophila Nanos

Genetics ◽  
1999 ◽  
Vol 153 (4) ◽  
pp. 1825-1838 ◽  
Author(s):  
Gustavo Arrizabalaga ◽  
Ruth Lehmann
Keyword(s):  
Cell Migration ◽  
Germ Cell ◽  
Protein Function ◽  
Germ Line ◽  
Primordial Germ Cells ◽  
Functional Domain ◽  
Embryonic Patterning ◽  
Tail Region ◽  
Germ Cell Migration ◽  
Drosophila Protein

AbstractThe Drosophila protein Nanos encodes an evolutionarily conserved protein with two zinc finger motifs. In the embryo, Nanos protein function is required for establishment of the anterior-posterior body pattern and for the migration of primordial germ cells. During oogenesis, Nanos protein is involved in the establishment and maintenance of germ-line stem cells and the differentiation of oocyte precursor cells. To establish proper embryonic patterning, Nanos acts as a translational regulator of hunchback RNA. Nanos' targets for germ cell migration and development are not known. Here, we describe a selective genetic screen aimed at isolating new nanos alleles. The molecular and genetic analysis of 68 new alleles has allowed us to identify amino acids critical for nanos function. This analysis shows that the CCHC motifs, which coordinate two metal ions, are essential for all known functions of Nanos protein. Furthermore, a region C-terminal to the zinc fingers seems to constitute a novel functional domain within the Nanos protein. This “tail region” of Nanos is required for abdomen formation and germ cell migration, but not for oogenesis.

Identification of X-Linked Genes Required for Migration and Programmed Cell Death of Drosophila melanogaster Germ Cells

Genetics ◽  
2002 ◽  
Vol 162 (1) ◽  
pp. 273-284 ◽  
Author(s):  
Clark R Coffman ◽  
Rachel C Strohm ◽  
Fredrick D Oakley ◽  
Yukiko Yamada ◽  
Danielle Przychodzin ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Migration ◽  
Germ Cell ◽  
Germ Cells ◽  
Posterior Pole ◽  
Developmentally Regulated ◽  
Regulated Cell Death ◽  
Somatic Gonad ◽  
Programmed Death ◽  
Germ Cell Migration

Abstract Drosophila germ cells form at the posterior pole of the embryo and migrate to the somatic gonad. Approximately 50% of the germ cells that form reach their target. The errant cells within the embryo undergo developmentally regulated cell death. Prior studies have identified some autosomal genes that regulate germ cell migration, but the genes that control germ cell death are not known. To identify X-linked genes required for germ cell migration and/or death, we performed a screen for mutations that disrupt these processes. Here we report the identification of scattershot and outsiders, two genes that regulate the programmed death of germ cells. The scattershot gene is defined by a mutation that disrupts both germ cell migration and the death of germ cells ectopic to the gonad. Maternal and zygotic expression of scattershot is required, but the migration and cell death functions can be genetically uncoupled. Zygotic expression of wild-type scattershot rescues germ cell pathfinding, but does not restore the programmed death of errant cells. The outsiders gene is required zygotically. In outsiders mutant embryos, the appropriate number of germ cells is incorporated into the gonad, but germ cells ectopic to the gonad persist.

scholarly journals ABC-transporter activity and autocrine eicosanoid-signaling are required for germ cell migration a basal chordate

2018 ◽  
Author(s):  
Susannah H. Kassmer ◽  
Delany Rodriguez ◽  
Anthony DeTomaso
Keyword(s):  
Arachidonic Acid ◽  
Cell Migration ◽  
Germ Cell ◽  
Abc Transporter ◽  
Germ Cells ◽  
Signaling Molecules ◽  
Germline Stem Cells ◽  
Colonial Ascidian ◽  
Germ Cell Migration ◽  
12 Lipoxygenase

AbstractIn the colonial ascidian Botryllus schlosseri, long-lived germline stem cells (GSCs) migrate to new germline niches as they develop during repetitive cycles of asexual reproduction. ABC-transporters are involved in the export of lipid-signaling molecules, but their roles in germ cell migration are poorly understood. Here, we show that in Botryllus, abcc1 and abcb1 are highly expressed in germ cells, and inhibition of ABC-transporter activity leads to failure of germ cell migration. Phospholipase A2 (PLA2) produces arachidonic acid, which is further metabolized to eicosanoid signaling molecules. In humans, 12-lipoxygenase (LOX) metabolizes arachidonic acid to12-Hydroxyeicosatetraenoic acid (12-S-HETE), which stimulates migration of mammalian cancer cells and smooth muscle cells. We show that PLA2 and LOX activity are required for germ cell migration. A potential homolog to the human receptor for 12-S-HETE, BSgpr31, is expressed in germ cells. 12-S-HETE rescues migration towards S1P in the presence of inhibitors of ABCC1, ABCB1, PLA2 or LOX, and a gradient of 12-S-HETE enhances chemotaxis towards S1P and stimulates motility. We conclude that 12-S-HETE is a secondary chemoattractant exported by ACB-transporters that is required for migration of germ cells towards S1P. We also find that in the presence of S1P, detection of an 12-S-HETE gradient initiates an autologous positive feedback loop that may sustain migration. This is the first report of an eicosanoid-signaling molecule regulating germ cell migration.

scholarly journals 50 years of spermatogenesis: Sertoli cells and their interactions with germ cells

2018 ◽  
Vol 99 (1) ◽  
pp. 87-100 ◽  
Author(s):  
Michael D Griswold
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Cultured Cells ◽  
Cell Types ◽  
Cell Development ◽  
Specific Cell ◽  
Germ Cell Development ◽  
Cell Niche ◽  
Transgenic Technologies

Abstract The complex morphology of the Sertoli cells and their interactions with germ cells has been a focus of investigators since they were first described by Enrico Sertoli. In the past 50 years, information on Sertoli cells has transcended morphology alone to become increasingly more focused on molecular questions. The goal of investigators has been to understand the role of the Sertoli cells in spermatogenesis and to apply that information to problems relating to male fertility. Sertoli cells are unique in that they are a nondividing cell population that is active for the reproductive lifetime of the animal and cyclically change morphology and gene expression. The numerous and distinctive junctional complexes and membrane specializations made by Sertoli cells provide a scaffold and environment for germ cell development. The increased focus of investigators on the molecular components and putative functions of testicular cells has resulted primarily from procedures that isolate specific cell types from the testicular milieu. Products of Sertoli cells that influence germ cell development and vice versa have been characterized from cultured cells and from the application of transgenic technologies. Germ cell transplantation has shown that the Sertoli cells respond to cues from germ cells with regard to developmental timing and has furthered a focus on spermatogenic stem cells and the stem cell niche. Very basic and universal features of spermatogenesis such as the cycle of the seminiferous epithelium and the spermatogenic wave are initiated by Sertoli cells and maintained by Sertoli-germ cell cooperation.

scholarly journals Hmgcr promotes a long-range signal to attract germ cells which is aided by Wunens but independent of hh

2018 ◽  
Author(s):  
Kim Kenwrick ◽  
Amrita Mukherjee ◽  
Andrew Renault
Keyword(s):  
Germ Cell ◽  
Long Range ◽  
Germ Cells ◽  
Cell Types ◽  
Final Position ◽  
Expression Of Genes ◽  
Germ Cell Migration ◽  
Summary Statement ◽  
Genetic Techniques ◽  
Native Context

Summary StatementMigrating Drosophila germ cells are attracted by a long range Hmgcr mediated signal which is aided and acts simultaneously with Wunens suggesting that these pathways converge on a single chemoattractant.AbstractIn a developing embryo, many cell types migrate from their point of specification to their final position. This usually involves highly stereotyped routes which are determined through deployment of cell surface or secreted guidance molecules. Whilst genetic techniques have been successful in identifying these molecules, the distances over which such signals operate in their native context can be difficult to determine. Here we have quantified the range of an attractive signal for the migration of Drosophila germ cells. Their migration is guided by an attractive signal generated by the expression of genes in the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (Hmgcr) pathway, and by a repulsive signal generated by the expression of Wunens. We demonstrate that the attractive signal downstream of Hmgcr operates over a long range and is sufficient to reach germ cells for the entirety of their migration. Furthermore, Hmgcr-mediated attraction and Wunen-mediated repulsion can operate simultaneously ruling out a model in which these pathways operate consecutively. Indeed, we show that Hmgcr-mediated attraction is boosted by Wunens suggesting the action of these two pathways is linked. Lastly, several papers have pointed to the secreted molecule Hedgehog (Hh) as being the germ cell attractant, whose secretion is increased by hmgcr. In this paper, we provide evidence that Hh is not downstream of hmgcr in germ cell migration.

Effects of 2,2',5,5'-tetrachlorobiphenyl (PCB52) on migration of chicken primordial germ cells

2005 ◽  
Vol 17 (5) ◽  
pp. 587 ◽  
Author(s):  
Yixiang Zhang ◽  
Xiumei Jin ◽  
Haitang Han ◽  
Zandong Li
Keyword(s):  
Cell Migration ◽  
Germ Cell ◽  
Germ Cells ◽  
Direct Action ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Initial Stage ◽  
Germ Cell Migration ◽  
Cell Migration And Proliferation ◽  
Migration And Development

Polychlorinated biphenyls cause developmental and physiological anomalies in the reproductive system. This study investigated the effects of 2,2′,5,5′-tetrachlorobiphenyl (PCB52), which can produce oestrogenic effects on the homeostasis of chicken primordial germ cells from the initial stage until completion of their settlement in the gonadal primordium. The blastoderm of chicken embryos was injected with 1 μL PCB52 (10 µmol/L) and oestradiol (100 µmol/L) before incubation, and the number of primordial germ cells was determined during their migration and development. The number of primordial germ cells in germinal crescents in PCB52-treated groups was slightly decreased (P = 0.068), but it was reduced significantly at stages 13–15 and 28–30 (P < 0.01, respectively) compared with controls. No obvious effects on primordial germ cell migration were observed with oestradiol treatments. The present results suggest that the influence of PCB52 on chicken primordial germ cell migration and proliferation may be via its toxic effect, not its oestrogen-mimicking effect, and provide information on the sensitivity of primordial germ cells to the direct action of PCB52.

Mouse primordial germ cells lacking beta1 integrins enter the germline but fail to migrate normally to the gonads

Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1655-1664 ◽  
Author(s):  
R. Anderson ◽  
R. Fassler ◽  
E. Georges-Labouesse ◽  
R.O. Hynes ◽  
B.L. Bader ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Migration ◽  
Germ Cell ◽  
Germ Cells ◽  
Fluorescent Protein ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Integrin Subunit ◽  
Integrin Beta1 ◽  
Germ Cell Migration

Primordial germ cells are the founder cells of the gametes. They are set aside at the initial stages of gastrulation in mammals, become embedded in the hind-gut endoderm, then actively migrate to the sites of gonad formation. The molecular basis of this migration is poorly understood. Here we sought to determine if members of the integrin family of cell surface receptors are required for primordial germ cell migration, as integrins have been implicated in the migration of several other motile cell types. We have established a line of mice which express green fluorescent protein in germline cells that has enabled us to efficiently purify primordial germ cells at different stages by flow cytometry. We have catalogued the spectrum of integrin subunit expression by primordial germ cells during and after migration, using flow cytometry, immunocytochemistry and RT-PCR. Through analysis of integrin beta1(−/−)--&gt;wild-type chimeras, we show that embryonic cells lacking beta1 integrins can enter the germline. However, integrin beta1(−/−) primordial germ cells do not colonize the gonad efficiently. Embryos with targeted deletion of integrin subunit alpha3, alpha6, or alphaV show no major defects in primordial germ cell migration. These results demonstrate a role for beta1-containing integrins in the development of the germline, although an equivalent role for * integrin subunit(s) has yet to be established.

scholarly journals Identification and Genetic Analysis of wunen, a Gene Guiding Drosophila melanogaster Germ Cell Migration

Genetics ◽  
1996 ◽  
Vol 143 (3) ◽  
pp. 1231-1241 ◽  
Author(s):  
Nian Zhang ◽  
Jiaping Zhang ◽  
Yan Cheng ◽  
Ken Howard
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Migration ◽  
Genetic Analysis ◽  
Germ Cell ◽  
Germ Cells ◽  
Germ Line ◽  
Genetic Locus ◽  
Somatic Gonad ◽  
Germ Cell Migration ◽  
Oriented Movement

Abstract We describe a novel genetic locus, wunen (wun), required for guidance of germ cell migration in early Drosophila development. Loss of wun function does not abolish movement but disrupts the orientation of the motion causing the germ cells to disperse even though their normal target, the somatic gonad, is well formed. We demonstrate that the product of this gene enables a signal to pass from the soma to the germ line and propose that the function of this signal is to selectively stabilize certain cytoplasmic extensions resulting in oriented movement. To characterize this guidance factor, we have mapped wun to within 100 kb of cloned DNA.

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