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  1. Article ; Online: Origin and development of neuropil glia of the Drosophila larval and adult brain: Two distinct glial populations derived from separate progenitors.

    Omoto, Jaison Jiro / Yogi, Puja / Hartenstein, Volker

    Developmental biology

    2015  Volume 404, Issue 2, Page(s) 2–20

    Abstract: Glia comprise a conspicuous population of non-neuronal cells in vertebrate and invertebrate nervous systems. Drosophila serves as a favorable model to elucidate basic principles of glial biology in vivo. The Drosophila neuropil glia (NPG), subdivided ... ...

    Abstract Glia comprise a conspicuous population of non-neuronal cells in vertebrate and invertebrate nervous systems. Drosophila serves as a favorable model to elucidate basic principles of glial biology in vivo. The Drosophila neuropil glia (NPG), subdivided into astrocyte-like (ALG) and ensheathing glia (EG), extend reticular processes which associate with synapses and sheath-like processes which surround neuropil compartments, respectively. In this paper we characterize the development of NPG throughout fly brain development. We find that differentiated neuropil glia of the larval brain originate as a cluster of precursors derived from embryonic progenitors located in the basal brain. These precursors undergo a characteristic migration to spread over the neuropil surface while specifying/differentiating into primary ALG and EG. Embryonically-derived primary NPG are large cells which are few in number, and occupy relatively stereotyped positions around the larval neuropil surface. During metamorphosis, primary NPG undergo cell death. Neuropil glia of the adult (secondary NPG) are derived from type II lineages during the postembryonic phase of neurogliogenesis. These secondary NPG are much smaller in size but greater in number than primary NPG. Lineage tracing reveals that both NPG subtypes derive from intermediate neural progenitors of multipotent type II lineages. Taken together, this study reveals previously uncharacterized dynamics of NPG development and provides a framework for future studies utilizing Drosophila glia as a model.
    MeSH term(s) Animals ; Astrocytes/cytology ; Brain/cytology ; Brain/embryology ; Cell Lineage ; Cell Movement ; Drosophila/embryology ; Larva/cytology ; Larva/growth & development ; Metamorphosis, Biological/physiology ; Neural Stem Cells/cytology ; Neurogenesis/physiology ; Neuroglia/cytology ; Neuropil/cytology
    Language English
    Publishing date 2015-03-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1114-9
    ISSN 1095-564X ; 0012-1606
    ISSN (online) 1095-564X
    ISSN 0012-1606
    DOI 10.1016/j.ydbio.2015.03.004
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  2. Article: Origin and development of neuropil glia of the Drosophila larval and adult brain: Two distinct glial populations derived from separate progenitors

    Omoto, Jaison Jiro / Yogi, Puja / Hartenstein, Volker

    Developmental biology. 2015 Aug. 15, v. 404, no. 2

    2015  

    Abstract: Glia comprise a conspicuous population of non-neuronal cells in vertebrate and invertebrate nervous systems. Drosophila serves as a favorable model to elucidate basic principles of glial biology in vivo. The Drosophila neuropil glia (NPG), subdivided ... ...

    Abstract Glia comprise a conspicuous population of non-neuronal cells in vertebrate and invertebrate nervous systems. Drosophila serves as a favorable model to elucidate basic principles of glial biology in vivo. The Drosophila neuropil glia (NPG), subdivided into astrocyte-like (ALG) and ensheathing glia (EG), extend reticular processes which associate with synapses and sheath-like processes which surround neuropil compartments, respectively. In this paper we characterize the development of NPG throughout fly brain development. We find that differentiated neuropil glia of the larval brain originate as a cluster of precursors derived from embryonic progenitors located in the basal brain. These precursors undergo a characteristic migration to spread over the neuropil surface while specifying/differentiating into primary ALG and EG. Embryonically-derived primary NPG are large cells which are few in number, and occupy relatively stereotyped positions around the larval neuropil surface. During metamorphosis, primary NPG undergo cell death. Neuropil glia of the adult (secondary NPG) are derived from type II lineages during the postembryonic phase of neurogliogenesis. These secondary NPG are much smaller in size but greater in number than primary NPG. Lineage tracing reveals that both NPG subtypes derive from intermediate neural progenitors of multipotent type II lineages. Taken together, this study reveals previously uncharacterized dynamics of NPG development and provides a framework for future studies utilizing Drosophila glia as a model.
    Keywords Drosophila ; adults ; brain ; cell death ; invertebrates ; larvae ; metamorphosis ; models ; synapse ; vertebrates
    Language English
    Dates of publication 2015-0815
    Size p. 2-20.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1114-9
    ISSN 1095-564X ; 0012-1606
    ISSN (online) 1095-564X
    ISSN 0012-1606
    DOI 10.1016/j.ydbio.2015.03.004
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  3. Article: Discovery and functional prioritization of Parkinson’s disease candidate genes from large-scale whole exome sequencing

    Jansen, Iris E / Amin, Najaf / Blauwendraat, Cornelis / Botia, Juan A / Brice, Alexis / Castillo-Lizardo, Melissa / Chouhan, Amit K / David, Della C / Drouet, Valérie / Gibbs, J. Raphael / Heetveld, Sasja / Heutink, Peter / Jain, Shushant / Lechler, Marie C / Lesage, Suzanne / Li, Yarong / Lubbe, Steven J / Majounie, Elisa / Michels, Helen /
    Morris, Huw R / Nalls, Mike A / Nollen, Ellen A / Rizzu, Patrizia / Ryten, Mina / Seinstra, Renée I / Shulman, Joshua M / Simon-Sanchez, Javier / Singleton, Andrew B / van Duijn, Cornelia M / Vandrovcova, Jana / Ye, Hui / Yogi, Puja

    Genome biology. 2017 Dec., v. 18, no. 1

    2017  

    Abstract: BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson’s disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD ... ...

    Institution International Parkinson’s Disease Genetics Consortium (IPGDC)
    Abstract BACKGROUND: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson’s disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. RESULTS: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes—GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C—also showed evidence consistent with genetic replication. CONCLUSIONS: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies.
    Keywords alleles ; cell culture ; data collection ; Drosophila ; heterozygosity ; homozygosity ; humans ; inheritance (genetics) ; loss-of-function mutation ; mitochondria ; models ; neurons ; Parkinson disease ; prioritization ; RNA interference ; sequence analysis
    Language English
    Dates of publication 2017-12
    Size p. 22.
    Publishing place BioMed Central
    Document type Article
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6914 ; 1465-6906
    ISSN (online) 1474-760X ; 1465-6914
    ISSN 1465-6906
    DOI 10.1186/s13059-017-1147-9
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Discovery and functional prioritization of Parkinson's disease candidate genes from large-scale whole exome sequencing.

    Jansen, Iris E / Ye, Hui / Heetveld, Sasja / Lechler, Marie C / Michels, Helen / Seinstra, Renée I / Lubbe, Steven J / Drouet, Valérie / Lesage, Suzanne / Majounie, Elisa / Gibbs, J Raphael / Nalls, Mike A / Ryten, Mina / Botia, Juan A / Vandrovcova, Jana / Simon-Sanchez, Javier / Castillo-Lizardo, Melissa / Rizzu, Patrizia / Blauwendraat, Cornelis /
    Chouhan, Amit K / Li, Yarong / Yogi, Puja / Amin, Najaf / van Duijn, Cornelia M / Morris, Huw R / Brice, Alexis / Singleton, Andrew B / David, Della C / Nollen, Ellen A / Jain, Shushant / Shulman, Joshua M / Heutink, Peter

    Genome biology

    2017  Volume 18, Issue 1, Page(s) 22

    Abstract: Background: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD ... ...

    Abstract Background: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models.
    Results: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication.
    Conclusions: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies.
    MeSH term(s) Adolescent ; Adult ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/genetics ; Case-Control Studies ; Cells, Cultured ; Child ; Disease Models, Animal ; Drosophila melanogaster/genetics ; Exome ; Genetic Predisposition to Disease ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Middle Aged ; Parkinson Disease/genetics ; RNA Interference ; Sequence Analysis, DNA/methods ; Young Adult ; alpha-Synuclein/genetics
    Chemical Substances alpha-Synuclein
    Language English
    Publishing date 2017-01-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1474-760X
    ISSN (online) 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-017-1147-9
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  5. Article ; Online: A functional genomics screen identifying blood cell development genes in Drosophila by undergraduates participating in a course-based research experience.

    Evans, Cory J / Olson, John M / Mondal, Bama Charan / Kandimalla, Pratyush / Abbasi, Ariano / Abdusamad, Mai M / Acosta, Osvaldo / Ainsworth, Julia A / Akram, Haris M / Albert, Ralph B / Alegria-Leal, Elitzander / Alexander, Kai Y / Ayala, Angelica C / Balashova, Nataliya S / Barber, Rebecca M / Bassi, Harmanjit / Bennion, Sean P / Beyder, Miriam / Bhatt, Kush V /
    Bhoot, Chinmay / Bradshaw, Aaron W / Brannigan, Tierney G / Cao, Boyu / Cashell, Yancey Y / Chai, Timothy / Chan, Alex W / Chan, Carissa / Chang, Inho / Chang, Jonathan / Chang, Michael T / Chang, Patrick W / Chang, Stephen / Chari, Neel / Chassiakos, Alexander J / Chen, Iris E / Chen, Vivian K / Chen, Zheying / Cheng, Marsha R / Chiang, Mimi / Chiu, Vivian / Choi, Sharon / Chung, Jun Ho / Contreras, Liset / Corona, Edgar / Cruz, Courtney J / Cruz, Renae L / Dang, Jefferson M / Dasari, Suhas P / De La Fuente, Justin R O / Del Rio, Oscar M A / Dennis, Emily R / Dertsakyan, Petros S / Dey, Ipsita / Distler, Rachel S / Dong, Zhiqiao / Dorman, Leah C / Douglass, Mark A / Ehresman, Allysen B / Fu, Ivy H / Fua, Andrea / Full, Sean M / Ghaffari-Rafi, Arash / Ghani, Asmar Abdul / Giap, Bosco / Gill, Sonia / Gill, Zafar S / Gills, Nicholas J / Godavarthi, Sindhuja / Golnazarian, Talin / Goyal, Raghav / Gray, Ricardo / Grunfeld, Alexander M / Gu, Kelly M / Gutierrez, Natalia C / Ha, An N / Hamid, Iman / Hanson, Ashley / Hao, Celesti / He, Chongbin / He, Mengshi / Hedtke, Joshua P / Hernandez, Ysrael K / Hlaing, Hnin / Hobby, Faith A / Hoi, Karen / Hope, Ashley C / Hosseinian, Sahra M / Hsu, Alice / Hsueh, Jennifer / Hu, Eileen / Hu, Spencer S / Huang, Stephanie / Huang, Wilson / Huynh, Melanie / Javier, Carmen / Jeon, Na Eun / Ji, Sunjong / Johal, Jasmin / John, Amala / Johnson, Lauren / Kadakia, Saurin / Kakade, Namrata / Kamel, Sarah / Kaur, Ravinder / Khatra, Jagteshwar S / Kho, Jeffrey A / Kim, Caleb / Kim, Emily Jin-Kyung / Kim, Hee Jong / Kim, Hyun Wook / Kim, Jin Hee / Kim, Seong Ah / Kim, Woo Kyeom / Kit, Brian / La, Cindy / Lai, Jonathan / Lam, Vivian / Le, Nguyen Khoi / Lee, Chi Ju / Lee, Dana / Lee, Dong Yeon / Lee, James / Lee, Jason / Lee, Jessica / Lee, Ju-Yeon / Lee, Sharon / Lee, Terrence C / Lee, Victoria / Li, Amber J / Li, Jialing / Libro, Alexandra M / Lien, Irvin C / Lim, Mia / Lin, Jeffrey M / Liu, Connie Y / Liu, Steven C / Louie, Irene / Lu, Shijia W / Luo, William Y / Luu, Tiffany / Madrigal, Josef T / Mai, Yishan / Miya, Darron I / Mohammadi, Mina / Mohanta, Sayonika / Mokwena, Tebogo / Montoya, Tonatiuh / Mould, Dallas L / Murata, Mark R / Muthaiya, Janani / Naicker, Seethim / Neebe, Mallory R / Ngo, Amy / Ngo, Duy Q / Ngo, Jamie A / Nguyen, Anh T / Nguyen, Huy C X / Nguyen, Rina H / Nguyen, Thao T T / Nguyen, Vincent T / Nishida, Kevin / Oh, Seo-Kyung / Omi, Kristen M / Onglatco, Mary C / Almazan, Guadalupe Ortega / Paguntalan, Jahzeel / Panchal, Maharshi / Pang, Stephanie / Parikh, Harin B / Patel, Purvi D / Patel, Trisha H / Petersen, Julia E / Pham, Steven / Phan-Everson, Tien M / Pokhriyal, Megha / Popovich, Davis W / Quaal, Adam T / Querubin, Karl / Resendiz, Anabel / Riabkova, Nadezhda / Rong, Fred / Salarkia, Sarah / Sama, Nateli / Sang, Elaine / Sanville, David A / Schoen, Emily R / Shen, Zhouyang / Siangchin, Ken / Sibal, Gabrielle / Sin, Garuem / Sjarif, Jasmine / Smith, Christopher J / Soeboer, Annisa N / Sosa, Cristian / Spitters, Derek / Stender, Bryan / Su, Chloe C / Summapund, Jenny / Sun, Beatrice J / Sutanto, Christine / Tan, Jaime S / Tan, Nguon L / Tangmatitam, Parich / Trac, Cindy K / Tran, Conny / Tran, Daniel / Tran, Duy / Tran, Vina / Truong, Patrick A / Tsai, Brandon L / Tsai, Pei-Hua / Tsui, C Kimberly / Uriu, Jackson K / Venkatesh, Sanan / Vo, Maique / Vo, Nhat-Thi / Vo, Phuong / Voros, Timothy C / Wan, Yuan / Wang, Eric / Wang, Jeffrey / Wang, Michael K / Wang, Yuxuan / Wei, Siman / Wilson, Matthew N / Wong, Daniel / Wu, Elliott / Xing, Hanning / Xu, Jason P / Yaftaly, Sahar / Yan, Kimberly / Yang, Evan / Yang, Rebecca / Yao, Tony / Yeo, Patricia / Yip, Vivian / Yogi, Puja / Young, Gloria Chin / Yung, Maggie M / Zai, Alexander / Zhang, Christine / Zhang, Xiao X / Zhao, Zijun / Zhou, Raymond / Zhou, Ziqi / Abutouk, Mona / Aguirre, Brian / Ao, Chon / Baranoff, Alexis / Beniwal, Angad / Cai, Zijie / Chan, Ryan / Chien, Kenneth Chang / Chaudhary, Umar / Chin, Patrick / Chowdhury, Praptee / Dalie, Jamlah / Du, Eric Y / Estrada, Alec / Feng, Erwin / Ghaly, Monica / Graf, Rose / Hernandez, Eduardo / Herrera, Kevin / Ho, Vivien W / Honeychurch, Kaitlyn / Hou, Yurianna / Huang, Jo M / Ishii, Momoko / James, Nicholas / Jang, Gah-Eun / Jin, Daphne / Juarez, Jesse / Kesaf, Ayse Elif / Khalsa, Sat Kartar / Kim, Hannah / Kovsky, Jenna / Kuang, Chak Lon / Kumar, Shraddha / Lam, Gloria / Lee, Ceejay / Lee, Grace / Li, Li / Lin, Joshua / Liu, Josephine / Ly, Janice / Ma, Austin / Markovic, Hannah / Medina, Cristian / Mungcal, Jonelle / Naranbaatar, Bilguudei / Patel, Kayla / Petersen, Lauren / Phan, Amanda / Phung, Malcolm / Priasti, Nadiyah / Ruano, Nancy / Salim, Tanveer / Schnell, Kristen / Shah, Paras / Shen, Jinhua / Stutzman, Nathan / Sukhina, Alisa / Tian, Rayna / Vega-Loza, Andrea / Wang, Joyce / Wang, Jun / Watanabe, Rina / Wei, Brandon / Xie, Lillian / Ye, Jessica / Zhao, Jeffrey / Zimmerman, Jill / Bracken, Colton / Capili, Jason / Char, Andrew / Chen, Michel / Huang, Pingdi / Ji, Sena / Kim, Emily / Kim, Kenneth / Ko, Julie / Laput, Sean Louise G / Law, Sam / Lee, Sang Kuk / Lee, Olivia / Lim, David / Lin, Eric / Marik, Kyle / Mytych, Josh / O'Laughlin, Andie / Pak, Jensen / Park, Claire / Ryu, Ruth / Shinde, Ashwin / Sosa, Manny / Waite, Nick / Williams, Mane / Wong, Richard / Woo, Jocelyn / Woo, Jonathan / Yepuri, Vishaal / Yim, Dorothy / Huynh, Dan / Wijiewarnasurya, Dinali / Shapiro, Casey / Levis-Fitzgerald, Marc / Jaworski, Leslie / Lopatto, David / Clark, Ira E / Johnson, Tracy / Banerjee, Utpal

    G3 (Bethesda, Md.)

    2021  Volume 11, Issue 1

    Abstract: Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes ... ...

    Abstract Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.
    MeSH term(s) Animals ; Blood Cells ; Drosophila/genetics ; Genomics/education ; Humans ; Students ; Universities
    Language English
    Publishing date 2021-02-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1093/g3journal/jkaa028
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