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198


Juvenile hormones direct primordial germ cell migration to the embryonic gonad

Barton, Lacy J; Sanny, Justina; Packard Dawson, Emily; Nouzova, Marcela; Noriega, Fernando Gabriel; Stadtfeld, Matthias; Lehmann, Ruth
Germ cells are essential to sexual reproduction. Across the animal kingdom, extracellular signaling isoprenoids, such as retinoic acids (RAs) in vertebrates and juvenile hormones (JHs) in invertebrates, facilitate multiple processes in reproduction. Here we investigated the role of these potent signaling molecules in embryonic germ cell development, using JHs in Drosophila melanogaster as a model system. In contrast to their established endocrine roles during larval and adult germline development, we found that JH signaling acts locally during embryonic development. Using an in vivo biosensor, we observed active JH signaling first within and near primordial germ cells (PGCs) as they migrate to the developing gonad. Through in vivo and in vitro assays, we determined that JHs are both necessary and sufficient for PGC migration. Analysis into the mechanisms of this newly uncovered paracrine JH function revealed that PGC migration was compromised when JHs were decreased or increased, suggesting that specific titers or spatiotemporal JH dynamics are required for robust PGC colonization of the gonad. Compromised PGC migration can impair fertility and cause germ cell tumors in many species, including humans. In mammals, retinoids have many roles in development and reproduction. We found that like JHs in Drosophila, RA was sufficient to impact mouse PGC migration in vitro. Together, our study reveals a previously unanticipated role of isoprenoids as local effectors of pre-gonadal PGC development and suggests a broadly shared mechanism in PGC migration.
PMID: 38215744
ISSN: 1879-0445
CID: 5633172

visMOP "“ A Visual Analytics Approach for Multi-omics Pathways

Brich, N.; Schacherer, N.; Hoene, M.; Weigert, C.; Lehmann, R.; Krone, M.
We present an approach for the visual analysis of multi-omics data obtained using high-throughput methods. The term "omics" denotes measurements of different types of biologically relevant molecules like the products of gene transcription (transcriptomics) or the abundance of proteins (proteomics). Current popular visualization approaches often only support analyzing each of these omics separately. This, however, disregards the interconnectedness of different biologically relevant molecules and processes. Consequently, it describes the actual events in the organism suboptimally or only partially. Our visual analytics approach for multi-omics data provides a comprehensive overview and details-on-demand by integrating the different omics types in multiple linked views. To give an overview, we map the measurements to known biological pathways and use a combination of a clustered network visualization, glyphs, and interactive filtering. To ensure the effectiveness and utility of our approach, we designed it in close collaboration with domain experts and assessed it using an exemplary workflow with real-world transcriptomics, proteomics, and lipidomics measurements from mice.
SCOPUS:85164273496
ISSN: 0167-7055
CID: 5548832

An AMPK phosphoregulated RhoGEF feedback loop tunes cortical flow-driven amoeboid migration in vivo

Lin, Benjamin; Luo, Jonathan; Lehmann, Ruth
Development, morphogenesis, immune system function, and cancer metastasis rely on the ability of cells to move through diverse tissues. To dissect migratory cell behavior in vivo, we developed cell type-specific imaging and perturbation techniques for Drosophila primordial germ cells (PGCs). We find that PGCs use global, retrograde cortical actin flows for orientation and propulsion during guided developmental homing. PGCs use RhoGEF2, a RhoA-specific RGS-RhoGEF, as a dose-dependent regulator of cortical flow through a feedback loop requiring its conserved PDZ and PH domains for membrane anchoring and local RhoA activation. This feedback loop is regulated for directional migration by RhoGEF2 availability and requires AMPK rather than canonical Gα12/13 signaling. AMPK multisite phosphorylation of RhoGEF2 near a conserved EB1 microtubule-binding SxIP motif releases RhoGEF2 from microtubule-dependent inhibition. Thus, we establish the mechanism by which global cortical flow and polarized RhoA activation can be dynamically adapted during natural cell navigation in a changing environment.
PMCID:9473612
PMID: 36103538
ISSN: 2375-2548
CID: 5332862

Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly

Li, Hongjie; Janssens, Jasper; De Waegeneer, Maxime; Kolluru, Sai Saroja; Davie, Kristofer; Gardeux, Vincent; Saelens, Wouter; David, Fabrice P A; Brbić, Maria; Spanier, Katina; Leskovec, Jure; McLaughlin, Colleen N; Xie, Qijing; Jones, Robert C; Brueckner, Katja; Shim, Jiwon; Tattikota, Sudhir Gopal; Schnorrer, Frank; Rust, Katja; Nystul, Todd G; Carvalho-Santos, Zita; Ribeiro, Carlos; Pal, Soumitra; Mahadevaraju, Sharvani; Przytycka, Teresa M; Allen, Aaron M; Goodwin, Stephen F; Berry, Cameron W; Fuller, Margaret T; White-Cooper, Helen; Matunis, Erika L; DiNardo, Stephen; Galenza, Anthony; O'Brien, Lucy Erin; Dow, Julian A T; Jasper, Heinrich; Oliver, Brian; Perrimon, Norbert; Deplancke, Bart; Quake, Stephen R; Luo, Liqun; Aerts, Stein; Agarwal, Devika; Ahmed-Braimah, Yasir; Arbeitman, Michelle; Ariss, Majd M; Augsburger, Jordan; Ayush, Kumar; Baker, Catherine C; Banisch, Torsten; Birker, Katja; Bodmer, Rolf; Bolival, Benjamin; Brantley, Susanna E; Brill, Julie A; Brown, Nora C; Buehner, Norene A; Cai, Xiaoyu Tracy; Cardoso-Figueiredo, Rita; Casares, Fernando; Chang, Amy; Clandinin, Thomas R; Crasta, Sheela; Desplan, Claude; Detweiler, Angela M; Dhakan, Darshan B; Donà, Erika; Engert, Stefanie; Floc'hlay, Swann; George, Nancy; González-Segarra, Amanda J; Groves, Andrew K; Gumbin, Samantha; Guo, Yanmeng; Harris, Devon E; Heifetz, Yael; Holtz, Stephen L; Horns, Felix; Hudry, Bruno; Hung, Ruei-Jiun; Jan, Yuh Nung; Jaszczak, Jacob S; Jefferis, Gregory S X E; Karkanias, Jim; Karr, Timothy L; Katheder, Nadja Sandra; Kezos, James; Kim, Anna A; Kim, Seung K; Kockel, Lutz; Konstantinides, Nikolaos; Kornberg, Thomas B; Krause, Henry M; Labott, Andrew Thomas; Laturney, Meghan; Lehmann, Ruth; Leinwand, Sarah; Li, Jiefu; Li, Joshua Shing Shun; Li, Kai; Li, Ke; Li, Liying; Li, Tun; Litovchenko, Maria; Liu, Han-Hsuan; Liu, Yifang; Lu, Tzu-Chiao; Manning, Jonathan; Mase, Anjeli; Matera-Vatnick, Mikaela; Matias, Neuza Reis; McDonough-Goldstein, Caitlin E; McGeever, Aaron; McLachlan, Alex D; Moreno-Roman, Paola; Neff, Norma; Neville, Megan; Ngo, Sang; Nielsen, Tanja; O'Brien, Caitlin E; Osumi-Sutherland, David; Özel, Mehmet Neset; Papatheodorou, Irene; Petkovic, Maja; Pilgrim, Clare; Pisco, Angela Oliveira; Reisenman, Carolina; Sanders, Erin Nicole; Dos Santos, Gilberto; Scott, Kristin; Sherlekar, Aparna; Shiu, Philip; Sims, David; Sit, Rene V; Slaidina, Maija; Smith, Harold E; Sterne, Gabriella; Su, Yu-Han; Sutton, Daniel; Tamayo, Marco; Tan, Michelle; Tastekin, Ibrahim; Treiber, Christoph; Vacek, David; Vogler, Georg; Waddell, Scott; Wang, Wanpeng; Wilson, Rachel I; Wolfner, Mariana F; Wong, Yiu-Cheung E; Xie, Anthony; Xu, Jun; Yamamoto, Shinya; Yan, Jia; Yao, Zepeng; Yoda, Kazuki; Zhu, Ruijun; Zinzen, Robert P
For more than 100 years, the fruit fly Drosophila melanogaster has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula Drosophilae, that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types between tissues, such as blood and muscle cells, reveals rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the Drosophila community and serves as a reference to study genetic perturbations and disease models at single-cell resolution.
PMID: 35239393
ISSN: 1095-9203
CID: 5174612

Large Drosophila germline piRNA clusters are evolutionarily labile and dispensable for transposon regulation

Gebert, Daniel; Neubert, Lena K; Lloyd, Catrin; Gui, Jinghua; Lehmann, Ruth; Teixeira, Felipe Karam
PIWI proteins and their guiding Piwi-interacting small RNAs (piRNAs) are crucial for fertility and transposon defense in the animal germline. In most species, the majority of piRNAs are produced from distinct large genomic loci, called piRNA clusters. It is assumed that germline-expressed piRNA clusters, particularly in Drosophila, act as principal regulators to control transposons dispersed across the genome. Here, using synteny analysis, we show that large clusters are evolutionarily labile, arise at loci characterized by recurrent chromosomal rearrangements, and are mostly species-specific across the Drosophila genus. By engineering chromosomal deletions in D. melanogaster, we demonstrate that the three largest germline clusters, which account for the accumulation of >40% of all transposon-targeting piRNAs in ovaries, are neither required for fertility nor for transposon regulation in trans. We provide further evidence that dispersed elements, rather than the regulatory action of large Drosophila germline clusters in trans, may be central for transposon defense.
PMID: 34352205
ISSN: 1097-4164
CID: 5026562

Model organism databases are in jeopardy

Bellen, Hugo J; Hubbard, E J A; Lehmann, Ruth; Madhani, Hiten D; Solnica-Krezel, Lila; Southard-Smith, E Michelle
PMID: 35231122
ISSN: 1477-9129
CID: 5174352

A single-cell atlas reveals unanticipated cell type complexity in Drosophila ovaries

Slaidina, Maija; Gupta, Selena; Banisch, Torsten U; Lehmann, Ruth
Organ function relies on the spatial organization and functional coordination of numerous cell types. The Drosophila ovary is a widely used model system to study the cellular activities underlying organ function, including stem cell regulation, cell signaling and epithelial morphogenesis. However, the relative paucity of cell type-specific reagents hinders investigation of molecular functions at the appropriate cellular resolution. Here, we used single-cell RNA sequencing to characterize all cell types of the stem cell compartment and early follicles of the Drosophila ovary. We computed transcriptional signatures and identified specific markers for nine states of germ cell differentiation and 23 somatic cell types and subtypes. We uncovered an unanticipated diversity of escort cells, the somatic cells that directly interact with differentiating germline cysts. Three escort cell subtypes reside in discrete anatomical positions and express distinct sets of secreted and transmembrane proteins, suggesting that diverse micro-environments support the progressive differentiation of germ cells. Finally, we identified 17 follicle cell subtypes and characterized their transcriptional profiles. Altogether, we provide a comprehensive resource of gene expression, cell type-specific markers, spatial coordinates, and functional predictions for 34 ovarian cell types and subtypes.
PMCID:8494228
PMID: 34389661
ISSN: 1549-5469
CID: 5061022

A transitory signaling center controls timing of primordial germ cell differentiation

Banisch, Torsten U; Slaidina, Maija; Gupta, Selena; Ho, Megan; Gilboa, Lilach; Lehmann, Ruth
Organogenesis requires exquisite spatiotemporal coordination of cell morphogenesis, migration, proliferation, and differentiation of multiple cell types. For gonads, this involves complex interactions between somatic and germline tissues. During Drosophila ovary morphogenesis, primordial germ cells (PGCs) either are sequestered in stem cell niches and are maintained in an undifferentiated germline stem cell state or transition directly toward differentiation. Here, we identify a mechanism that links hormonal triggers of somatic tissue morphogenesis with PGC differentiation. An early ecdysone pulse initiates somatic swarm cell (SwC) migration, positioning these cells close to PGCs. A second hormone peak activates Torso-like signal in SwCs, which stimulates the Torso receptor tyrosine kinase (RTK) signaling pathway in PGCs promoting their differentiation by de-repression of the differentiation gene, bag of marbles. Thus, systemic temporal cues generate a transitory signaling center that coordinates ovarian morphogenesis with stem cell self-renewal and differentiation programs, highlighting a more general role for such centers in reproductive and developmental biology.
PMID: 34081907
ISSN: 1878-1551
CID: 4891912

In Memoriam: Kathryn V. Anderson (1952-2020)

Joyner, Alex; Lehmann, Ruth; Niswander, Lee
PMID: 33618188
ISSN: 1095-564x
CID: 4794302

Angelika Amon (1967-2020)

Lehmann, Ruth; Peters, Jan-Michael
PMID: 33417858
ISSN: 1097-4172
CID: 4739462