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Article ; Online: Proximal tibial extra-axial chordoma masquerading as renal cell carcinoma metastasis.

Huang, Jennifer / Bhojwani, Nicholas / Oakley, Fredrick D / Jordanov, Martin I

2017 Volume 46, Issue 11, Page(s) 1567–1573

Abstract: Chordomas are rare, locally aggressive notochordal tumors, which most frequently occur in the neuraxis. We describe the case of a 74-year-old male with a history of renal cell carcinoma, who presented with a slowly enlarging mass in his left leg. While ... ...

Abstract	Chordomas are rare, locally aggressive notochordal tumors, which most frequently occur in the neuraxis. We describe the case of a 74-year-old male with a history of renal cell carcinoma, who presented with a slowly enlarging mass in his left leg. While the clinical history and imaging suggested metastatic renal cell carcinoma, immunohistochemical staining with brachyury ultimately made the diagnosis of extra-axial chordoma. At 74 years of age, our patient is the oldest ever reported with bony extra-axial chordoma objectively confirmed by brachyury staining. A detailed case discussion and a review of the available literature on this rare clinicopathologic entity are provided.
Language	English
Publishing date	2017-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	527592-1
ISSN	1432-2161 ; 0364-2348
ISSN (online)	1432-2161
ISSN	0364-2348
DOI	10.1007/s00256-017-2711-9
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Article ; Online: Next-Generation Sequencing (NGS) Methods Show Superior or Equivalent Performance to Non-NGS Methods on

Surrey, Lea F / Oakley, Fredrick D / Merker, Jason D / Long, Thomas A / Vasalos, Patricia / Moncur, Joel T / Kim, Annette S

Archives of pathology & laboratory medicine

2019 Volume 143, Issue 8, Page(s) 980–984

Abstract: Context.—: There has been a rapid expansion of next-generation sequencing (NGS)-based assays for the detection of somatic variants in solid tumors. However, limited data are available regarding the comparative performance of NGS and non-NGS assays using ...

Abstract	Context.—: There has been a rapid expansion of next-generation sequencing (NGS)-based assays for the detection of somatic variants in solid tumors. However, limited data are available regarding the comparative performance of NGS and non-NGS assays using standardized samples across a large number of laboratories. Objective.—: To compare the performance of NGS and non-NGS assays using well-characterized proficiency testing samples provided by the College of American Pathologists (CAP) Molecular Oncology Committee. A secondary goal was to compare the use of preanalytic and postanalytic practices. Design.—: A total of 17 343 responses were obtained from participants in the Results.—: While both NGS and non-NGS achieved an acceptable response rate of greater than 95%, the overall performance of NGS methods was significantly better than that of non-NGS methods for the identification of variants in Conclusions.—: The overall analytic performance of both methods was excellent. For specific
MeSH term(s)	ErbB Receptors/genetics ; Genetic Testing/methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Laboratory Proficiency Testing/methods ; Mutation ; Neoplasms/diagnosis ; Neoplasms/genetics ; Neoplasms/pathology ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins p21(ras)/genetics ; Reproducibility of Results ; Sensitivity and Specificity
Chemical Substances	KRAS protein, human ; EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2019-03-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	194119-7
ISSN	1543-2165 ; 0363-0153 ; 0096-8528 ; 0003-9985
ISSN (online)	1543-2165
ISSN	0363-0153 ; 0096-8528 ; 0003-9985
DOI	10.5858/arpa.2018-0394-CP
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Article ; Online: Transfusion reactions in pediatric compared with adult patients: a look at rate, reaction type, and associated products.

Oakley, Fredrick D / Woods, Marcella / Arnold, Shanna / Young, Pampee P

Transfusion

2014 Volume 55, Issue 3, Page(s) 563–570

Abstract: Background: The majority of reports on transfusion reactions address adult patients. Less is known about the types, incidence, and other clinical details of transfusion reactions in pediatric populations. Furthermore, to our knowledge, there have been ... ...

Abstract	Background: The majority of reports on transfusion reactions address adult patients. Less is known about the types, incidence, and other clinical details of transfusion reactions in pediatric populations. Furthermore, to our knowledge, there have been no previous reports directly comparing these aspects between adults and pediatric patient populations to assess if there are differences. Study design and methods: Between the period of January 1, 2011, and February 1, 2013, all reported adult and pediatric transfusion reactions at Vanderbilt University Medical Center (VUMC) were evaluated by transfusion medicine clinical service. The information was subsequently shared with the hemovigilance database. Data provided to hemovigilance included age, sex, blood product associated with the reaction, severity of the reaction, and the type of transfusion reactions. These were collated with hospital and blood bank information system-acquired data on overall admission and product transfusion. Results: A total of 133,671 transfusions were performed at VUMC during the study period including 20,179 platelet (PLT) transfusions, 31,605 plasma transfusions, 79,933 red blood cell (RBC) transfusions, and 2154 cryoprecipitate transfusions. Over the same period, 108 pediatric and 277 adult transfusion reactions were recorded. This corresponds to an incidence of 6.2 reactions per 1000 transfusions within the pediatric (age < 21) population and an incidence of 2.4 reactions per 1000 transfusions within the adult population. In both adult and pediatric populations, transfusion reactions were most commonly associated with PLT, followed by RBC, and then plasma transfusions. Within the pediatric population, subset analysis identified multiple differences when compared to the adult population, including an increased incidence of allergic transfusion reactions (2.7/1000 vs. 1.1/1000, p < 0.001), febrile nonhemolytic transfusion reactions (1.9/1000 vs. 0.47/1000, p < 0.001), and hypotensive transfusion reactions (0.29/1000 vs. 0.078/1000, p < 0.05). Interestingly, while the reaction incidence was the same between sexes in adults, in pediatric patients, reactions were more common in male patients (7.9/1000 pediatric males vs. 4.3/1000 pediatric females, p < 0.01). Conclusion: To our knowledge this is the first study to provide detailed comparisons of acute transfusion reactions to all blood products between pediatric and adult populations at a single institution and supported by a single transfusion service and culture. Collectively these data provide insight into pediatric transfusion reactions and demonstrate a general increase in the incidence of transfusion reactions within the pediatric compared to adult population.
MeSH term(s)	Acute Lung Injury/epidemiology ; Acute Lung Injury/etiology ; Adult ; Age Distribution ; Age of Onset ; Blood Component Transfusion/adverse effects ; Blood Group Incompatibility/epidemiology ; Blood Group Incompatibility/etiology ; Blood Safety ; Child ; Factor VIII/adverse effects ; Female ; Fibrinogen/adverse effects ; Humans ; Hypotension/epidemiology ; Hypotension/etiology ; Incidence ; Male ; Plasma ; Prospective Studies ; Sex Distribution ; Shock/epidemiology ; Shock/etiology ; Tennessee/epidemiology ; Transfusion Reaction/classification ; Transfusion Reaction/epidemiology ; Transfusion Reaction/etiology
Chemical Substances	cryoprecipitate coagulum ; Factor VIII (9001-27-8) ; Fibrinogen (9001-32-5)
Language	English
Publishing date	2014-08-22
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.12827
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Article ; Online: The impact of tumor size in breast needle biopsy material on final pathologic size and tumor stage: a detailed analysis of 222 consecutive cases.

Edwards, Henry D / Oakley, Fredrick / Koyama, Tatsuki / Hameed, Omar

The American journal of surgical pathology

2013 Volume 37, Issue 5, Page(s) 739–744

Abstract: Tumor size is a significant prognostic indicator for invasive mammary carcinoma. By current standards, this is routinely reported during pathologic evaluation of the definitive excision, but no recommendations exist for reporting tumor size in needle ... ...

Abstract	Tumor size is a significant prognostic indicator for invasive mammary carcinoma. By current standards, this is routinely reported during pathologic evaluation of the definitive excision, but no recommendations exist for reporting tumor size in needle biopsy material. The purpose of this study is to evaluate the relationship between tumor size on breast needle biopsy specimens and that on subsequent definitive excision specimens and to evaluate the impact of the former, if any, in determining the final pathologic tumor stage. This was achieved by an evaluation of 222 consecutive cases of invasive mammary carcinoma for which both the diagnostic biopsy and definitive excision were available for review. Of 200 cases without a history of neoadjuvant therapy, there were 161 (80.5%) cases in which the tumor size on biopsy was smaller, 15 (7.5%) cases in which the sizes were equal, and 24 (12%) in which the size on biopsy was greater, including 6 (3%) cases with no residual tumor on excision. The average size change (excision size minus biopsy size) increased with increasing tumor stage, with these being significantly lower in pT1a compared with pT1b tumors (-0.14 vs. 0.17 mm; P=0.0002), pT1a/b compared with pT1c tumors (0.12 vs. 0.53 mm; P<0.0001), and pT1 compared with pT2/3 tumors (0.32 vs. 2.2 mm; P<0.001). Of the 24 cases in which tumor size on biopsy was greater than that on excision, there were 15 (7.5% of cohort) in which the tumor size on biopsy was the sole determinant of a higher final pathologic T stage. A larger tumor size on biopsy compared with that on excision was significantly associated with a lower final pathologic T stage (P<0.001) but not with patient age, histologic type, histologic grade, mitotic score, or the presence/absence of ductal carcinoma in situ. Evaluation of the remaining 22 cases also showed that there was a clear association between a history of neoadjuvant therapy and the finding of a larger size on biopsy compared with that on excision (P<0.0001). These findings indicate that tumor size on breast needle biopsy is not infrequently larger than that on excision and can also dictate the final pathologic T stage. Accordingly, it is recommended that the greatest extent of invasive carcinoma is reported in all needle biopsy specimens.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Breast Neoplasms/pathology ; Carcinoma/pathology ; Female ; Humans ; Middle Aged ; Neoplasm Staging/methods ; Prognosis ; Young Adult
Language	English
Publishing date	2013-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	752964-8
ISSN	1532-0979 ; 0147-5185
ISSN (online)	1532-0979
ISSN	0147-5185
DOI	10.1097/PAS.0b013e31828c63d0
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Article ; Online: Lipid rafts and caveolin-1 coordinate interleukin-1beta (IL-1beta)-dependent activation of NFkappaB by controlling endocytosis of Nox2 and IL-1beta receptor 1 from the plasma membrane.

Oakley, Fredrick D / Smith, Rachel L / Engelhardt, John F

The Journal of biological chemistry

2009 Volume 284, Issue 48, Page(s) 33255–33264

Abstract: Recent evidence suggests that signaling by the proinflammatory cytokine interleukin-1beta (IL-1beta) is dependent on reactive oxygen species derived from NADPH oxidase. Redox signaling in response to IL-1beta is known to require endocytosis of its ... ...

Abstract	Recent evidence suggests that signaling by the proinflammatory cytokine interleukin-1beta (IL-1beta) is dependent on reactive oxygen species derived from NADPH oxidase. Redox signaling in response to IL-1beta is known to require endocytosis of its cognate receptor (IL-1R1) following ligand binding and the formation of redox-active signaling endosomes that contain Nox2 (also called redoxosomes). The consequent generation of reactive oxygen species by redoxosomes is responsible for the downstream recruitment of IL-1R1 effectors (IRAK, TRAF6, and IkappaB kinase kinases) and ultimately for activation of the transcription factor NFkappaB. Despite this knowledge of the signaling events that occur downstream of redoxosome formation, an understanding of the mechanisms that coordinate the genesis of redoxosomes following IL-1beta stimulation has been lacking. Here, we demonstrate that lipid rafts play an important role in this process. We show that Nox2 and IL-1R1 localize to plasma membrane lipid rafts in the unstimulated state and that IL-1beta signals caveolin-1-dependent endocytosis of both proteins into the redoxosome. We also show that inhibiting lipid raft-mediated endocytosis prevents NFkappaB activation. Finally, we demonstrate that Vav1, a Rac1 guanine exchange factor and activator of Nox2, is recruited to lipid rafts following IL-1beta stimulation and that it is required for NFkappaB activation. Our results fill in an important mechanistic gap in the understanding of early IL-1R1 and Nox2 signaling events that control NFkappaB activation, a redox-dependent process important in inflammation.
MeSH term(s)	Animals ; Caveolin 1/genetics ; Caveolin 1/metabolism ; Cell Line, Tumor ; Cell Membrane/metabolism ; Cells, Cultured ; Endocytosis/drug effects ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Humans ; Immunoblotting ; Interleukin-1beta/pharmacology ; Luciferases/genetics ; Luciferases/metabolism ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Membrane Microdomains/metabolism ; Mice ; Mice, Knockout ; Microscopy, Confocal ; NADPH Oxidase 2 ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Proto-Oncogene Proteins c-vav/genetics ; Proto-Oncogene Proteins c-vav/metabolism ; Receptors, Interleukin-1/genetics ; Receptors, Interleukin-1/metabolism ; Signal Transduction/drug effects
Chemical Substances	Caveolin 1 ; Interleukin-1beta ; Membrane Glycoproteins ; NF-kappa B ; Proto-Oncogene Proteins c-vav ; Receptors, Interleukin-1 ; VAV1 protein, human ; Green Fluorescent Proteins (147336-22-9) ; Luciferases (EC 1.13.12.-) ; CYBB protein, human (EC 1.6.3.-) ; NADPH Oxidase 2 (EC 1.6.3.-) ; NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2009-10-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M109.042127
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Article: Lipid Rafts and Caveolin-1 Coordinate Interleukin-1β (IL-1β)-dependent Activation of NFκB by Controlling Endocytosis of Nox2 and IL-1β Receptor 1 from the Plasma Membrane

Oakley, Fredrick D / Smith, Rachel L / Engelhardt, John F

Journal of biological chemistry. 2009 Nov. 27, v. 284, no. 48

2009

Abstract: Recent evidence suggests that signaling by the proinflammatory cytokine interleukin-1β (IL-1β) is dependent on reactive oxygen species derived from NADPH oxidase. Redox signaling in response to IL-1β is known to require endocytosis of its cognate ... ...

Abstract	Recent evidence suggests that signaling by the proinflammatory cytokine interleukin-1β (IL-1β) is dependent on reactive oxygen species derived from NADPH oxidase. Redox signaling in response to IL-1β is known to require endocytosis of its cognate receptor (IL-1R1) following ligand binding and the formation of redox-active signaling endosomes that contain Nox2 (also called redoxosomes). The consequent generation of reactive oxygen species by redoxosomes is responsible for the downstream recruitment of IL-1R1 effectors (IRAK, TRAF6, and IκB kinase kinases) and ultimately for activation of the transcription factor NFκB. Despite this knowledge of the signaling events that occur downstream of redoxosome formation, an understanding of the mechanisms that coordinate the genesis of redoxosomes following IL-1β stimulation has been lacking. Here, we demonstrate that lipid rafts play an important role in this process. We show that Nox2 and IL-1R1 localize to plasma membrane lipid rafts in the unstimulated state and that IL-1β signals caveolin-1-dependent endocytosis of both proteins into the redoxosome. We also show that inhibiting lipid raft-mediated endocytosis prevents NFκB activation. Finally, we demonstrate that Vav1, a Rac1 guanine exchange factor and activator of Nox2, is recruited to lipid rafts following IL-1β stimulation and that it is required for NFκB activation. Our results fill in an important mechanistic gap in the understanding of early IL-1R1 and Nox2 signaling events that control NFκB activation, a redox-dependent process important in inflammation.
Language	English
Dates of publication	2009-1127
Size	p. 33255-33264.
Publishing place	American Society for Biochemistry and Molecular Biology
Document type	Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Signaling components of redox active endosomes: the redoxosomes.

Oakley, Fredrick D / Abbott, Duane / Li, Qiang / Engelhardt, John F

Antioxidants & redox signaling

2006 Volume 11, Issue 6, Page(s) 1313–1333

Abstract: Subcellular compartmentalization of reactive oxygen species (ROS) plays a critical role in transmitting cell signals in response to environmental stimuli. In this regard, signals at the plasma membrane have been shown to trigger NADPH oxidase-dependent ... ...

Abstract	Subcellular compartmentalization of reactive oxygen species (ROS) plays a critical role in transmitting cell signals in response to environmental stimuli. In this regard, signals at the plasma membrane have been shown to trigger NADPH oxidase-dependent ROS production within the endosomal compartment and this step can be required for redox-dependent signal transduction. Unique features of redox-active signaling endosomes can include NADPH oxidase complex components (Nox1, Noxo1, Noxa1, Nox2, p47phox, p67phox, and/or Rac1), ROS processing enzymes (SOD1 and/or peroxiredoxins), chloride channels capable of mediating superoxide transport and/or membrane gradients required for Nox activity, and novel redox-dependent sensors that control Nox activity. This review will discuss the cytokine and growth factor receptors that likely mediate signaling through redox-active endosomes, and the common mechanisms whereby they act. Additionally, the review will cover ligand-independent environmental injuries, such as hypoxia/reoxygenation injury, that also appear to facilitate cell signaling through NADPH oxidase at the level of the endosome. We suggest that redox-active endosomes encompass a subset of signaling endosomes that we have termed redoxosomes. Redoxosomes are uniquely equipped with redox-processing proteins capable of transmitting ROS signals from the endosome interior to redox-sensitive effectors on the endosomal surface. In this manner, redoxosomes can control redox-dependent effector functions through the spatial and temporal regulation of ROS as second messengers.
MeSH term(s)	Animals ; Endosomes/metabolism ; Humans ; NADPH Oxidases/metabolism ; Oxidation-Reduction ; Reactive Oxygen Species/metabolism ; Signal Transduction/physiology
Chemical Substances	Reactive Oxygen Species ; NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2006-12-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ARS.2008.2363
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Article ; Online: Endosomal Nox2 facilitates redox-dependent induction of NF-kappaB by TNF-alpha.

Li, Qiang / Spencer, Netanya Y / Oakley, Fredrick D / Buettner, Garry R / Engelhardt, John F

Antioxidants & redox signaling

2008 Volume 11, Issue 6, Page(s) 1249–1263

Abstract: Growing evidence suggests that NADPH oxidase (Nox)-derived reactive oxygen species (ROS) play important roles in regulating cytokine signaling. We have explored how TNF-alpha induction of Nox-dependent ROS influences NF-kappaB activation. Cellular ... ...

Abstract	Growing evidence suggests that NADPH oxidase (Nox)-derived reactive oxygen species (ROS) play important roles in regulating cytokine signaling. We have explored how TNF-alpha induction of Nox-dependent ROS influences NF-kappaB activation. Cellular stimulation by TNF-alpha induced NADPH-dependent superoxide production in the endosomal compartment, and this ROS was required for IKK-mediated activation of NF-kappaB. Inhibiting endocytosis reduced the ability of TNF-alpha to induce both NADPH-dependent endosomal superoxide and NF-kappaB, supporting the notion that redox-dependent signaling of the receptor occurs in the endosome. Molecular analyses demonstrated that endosomal H(2)O(2) was critical for the recruitment of TRAF2 to the TNFR1/TRADD complex after endocytosis. Studies using both Nox2 siRNA and Nox2-knockout primary fibroblasts indicated that Nox2 was critical for TNF-alpha-mediated induction of endosomal superoxide. Redox-active endosomes that form after TNF-alpha or IL-1 beta induction recruit several common proteins (Rac1, Nox2, p67(phox), SOD1), while also retaining specificity for ligand-activated receptor effectors. Our studies suggest that TNF-alpha and IL-1 beta signaling pathways both can use Nox2 to facilitate redox activation of their respective receptors at the endosomal level by promoting the redox-dependent recruitment of TRAFs. These studies help to explain how cellular compartmentalization of redox signals can be used to direct receptor activation from the plasma membrane.
MeSH term(s)	Animals ; Blotting, Western ; Catalase/pharmacology ; Cell Line, Tumor ; Cells, Cultured ; Dynamins/metabolism ; Endocytosis/physiology ; Endosomes/enzymology ; Endosomes/metabolism ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Glutathione Peroxidase/genetics ; Glutathione Peroxidase/physiology ; Humans ; Immunoprecipitation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism ; NF-kappa B/metabolism ; Oxidation-Reduction/drug effects ; RNA, Small Interfering ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/pharmacology ; Superoxide Dismutase-1 ; Superoxides/metabolism ; TNF Receptor-Associated Factor 2/metabolism ; Tumor Necrosis Factor-alpha/pharmacology
Chemical Substances	NF-kappa B ; RNA, Small Interfering ; Reactive Oxygen Species ; SOD1 protein, human ; TNF Receptor-Associated Factor 2 ; Tumor Necrosis Factor-alpha ; Superoxides (11062-77-4) ; glutathione peroxidase GPX1 (EC 1.11.1.-) ; Catalase (EC 1.11.1.6) ; Glutathione Peroxidase (EC 1.11.1.9) ; Sod1 protein, mouse (EC 1.15.1.1) ; Superoxide Dismutase (EC 1.15.1.1) ; Superoxide Dismutase-1 (EC 1.15.1.1) ; NADPH Oxidases (EC 1.6.3.-) ; Dynamins (EC 3.6.5.5)
Language	English
Publishing date	2008-12-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ARS.2008.2407
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Article: Comparative EST analyses in plant systems.

Dong, Qunfeng / Kroiss, Lori / Oakley, Fredrick D / Wang, Bing-Bing / Brendel, Volker

Methods in enzymology

2005 Volume 395, Page(s) 400–418

Abstract: Expressed sequence tag (EST) data are a major contributor to the known plant sequence space. Organization of the data into non-redundant clusters representing tentative unique genes provides snapshots of the gene repertoires of a species. This chapter ... ...

Abstract	Expressed sequence tag (EST) data are a major contributor to the known plant sequence space. Organization of the data into non-redundant clusters representing tentative unique genes provides snapshots of the gene repertoires of a species. This chapter reviews availability of sequences and sequence analysis results and describes several resources and tools that should facilitate broad-based utilization of EST data for gene structure annotation, gene discovery, and comparative genomics.
MeSH term(s)	Alternative Splicing ; Base Sequence ; Conserved Sequence ; DNA, Complementary/genetics ; DNA, Plant/genetics ; Databases, Genetic ; Expressed Sequence Tags ; Gene Library ; Genes, Plant ; Genomics/methods ; Molecular Sequence Data ; Multigene Family ; Plants/genetics ; Sequence Alignment/methods
Chemical Substances	DNA, Complementary ; DNA, Plant
Language	English
Publishing date	2005
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ISSN	0076-6879
ISSN	0076-6879
DOI	10.1016/s0076-6879(05)95022-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Identification of X-linked genes required for migration and programmed cell death of Drosophila melanogaster germ cells.

Coffman, Clark R / Strohm, Rachel C / Oakley, Fredrick D / Yamada, Yukiko / Przychodzin, Danielle / Boswell, Robert E

Genetics

2001 Volume 162, Issue 1, Page(s) 273–284

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 ... ...

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.
MeSH term(s)	Animals ; Apoptosis/genetics ; Cell Movement/genetics ; Drosophila melanogaster/cytology ; Drosophila melanogaster/genetics ; Genetic Complementation Test ; Genetic Linkage ; Germ Cells/cytology ; X Chromosome
Language	English
Publishing date	2001-02-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2167-2
ISSN	1943-2631 ; 0016-6731
ISSN (online)	1943-2631
ISSN	0016-6731
DOI	10.1093/genetics/162.1.273
Database	MEDical Literature Analysis and Retrieval System OnLINE

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