[{"type":"preprint","abstract":[{"text":"The development, evolution, and function of the vertebrate central nervous system (CNS) can be best studied using diverse model organisms. Amphibians, with their unique phylogenetic position at the transition between aquatic and terrestrial lifestyles, are valuable for understanding the origin and evolution of the tetrapod brain and spinal cord. Their metamorphic developmental transitions and unique regenerative abilities also facilitate the discovery of mechanisms for neural circuit remodeling and replacement. The genetic toolkit for amphibians, however, remains limited, with only a few species having sequenced genomes and a small number of transgenic lines available. In mammals, recombinant adeno-associated viral vectors (AAVs) have become a powerful alternative to genome modification for visualizing and perturbing the nervous system. AAVs are DNA viruses that enable neuronal transduction in both developing and adult animals with low toxicity and spatial, temporal, and cell-type specificity. However, AAVs have never been shown to transduce amphibian cells efficiently. To bridge this gap, we established a simple, scalable, and robust strategy to screen AAV serotypes in three distantly-related amphibian species: the frogs Xenopus laevis and Pelophylax bedriagae, and the salamander Pleurodeles waltl, in both developing larval tadpoles and post-metamorphic animals. For each species, we successfully identified at least two AAV serotypes capable of infecting the CNS; however, no pan-amphibian serotype was identified, indicating rapid evolution of AAV tropism. In addition, we developed an AAV-based strategy that targets isochronic cohorts of developing neurons – a critical tool for parsing neural circuit assembly. Finally, to enable visualization and manipulation of neural circuits, we identified AAV variants for retrograde tracing of neuronal projections in adult animals. Our findings expand the toolkit for amphibians to include AAVs, establish a generalizable workflow for AAV screening in non-canonical research organisms, generate testable hypotheses for the evolution of AAV tropism, and lay the foundation for modern cross-species comparisons of vertebrate CNS development, function, and evolution. ","lang":"eng"}],"department":[{"_id":"LoSw"},{"_id":"MaDe"},{"_id":"GaNo"}],"status":"public","publication_status":"submitted","title":"Adeno-associated viral tools to trace neural development and connectivity across amphibians","_id":"15016","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2024","acknowledgement":"We would like to extend our thanks to members of the Sweeney, Tosches, Shein-Idelson,\r\nYamaguchi, Kelley, and Cline Labs for their contributions to this project, discussion and support.\r\nWe additionally thank the Beckman Institute Clover Center and Viviana Gradinaru (Caltech),\r\nKimberly Ritola (UNC NeuroTools), Flavia Gama Gomez Leite (ISTA Viral Core), and Hüseyin\r\nCihan Önal (Shigemoto Group, ISTA) for their consultation and assistance regarding AAVs, as\r\nwell as Andras Simon and Alberto Joven for feedback and discussions on AAVs in Pleurodeles.\r\nTo do these experiments, we have also benefited from the tremendous support of our animal care and imaging facilities at our respective institutions, as well as the amphibian stock centers\r\n(National Xenopus Resource Center, European Xenopus Resource Center, Xenopus Express)\r\nand our funding sources: U.S. National Science Foundation (NSF) Grant Number IOS 2110086\r\n(D.B.K., L.B.S., M.A.T., A.Y., and H.T.C.); United States-Israel Binational Science Foundation\r\n(BSF) Grant Number 2020702 (M.S.-I.); NSF Award Number 1645105 (G.J.G., M.E.H.); FTI\r\nStrategy Lower Austria Dissertation Grant Number FTI21-D-046 (D.V.); Horizon Europe ERC\r\nStarting Grant Number 101041551 (L.B.S.); NIH grant number R35GM146973 (M.A.T.); Rita Allen\r\nFoundation award number GA_032522_FE (M.A.T.); European Molecular Biology Organization\r\nLong-Term Fellowship ALTF 874-2021 (A.D.); National Science Foundation Graduate Research\r\nFellowship DGE 2036197 (E.C.J.B.); NIH grant number P40OD010997 (M.E.H).","oa_version":"Preprint","date_created":"2024-02-20T09:20:32Z","date_updated":"2024-02-20T09:34:25Z","author":[{"full_name":"Jaeger, Eliza C.B.","first_name":"Eliza C.B.","last_name":"Jaeger"},{"id":"cf391e77-ec3c-11ea-a124-d69323410b58","first_name":"David","last_name":"Vijatovic","full_name":"Vijatovic, David"},{"last_name":"Deryckere","first_name":"Astrid","full_name":"Deryckere, Astrid"},{"last_name":"Zorin","first_name":"Nikol","full_name":"Zorin, Nikol"},{"full_name":"Nguyen, Akemi L.","last_name":"Nguyen","first_name":"Akemi L."},{"full_name":"Ivanian, Georgiy","first_name":"Georgiy","last_name":"Ivanian","id":"eaf2b366-cfd1-11ee-bbdf-c8790f800a05"},{"full_name":"Woych, Jamie","last_name":"Woych","first_name":"Jamie"},{"id":"d6cce458-14c9-11ed-a755-c1c8fc6fde6f","first_name":"Rebecca C","last_name":"Arnold","full_name":"Arnold, Rebecca C"},{"first_name":"Alonso","last_name":"Ortega Gurrola","full_name":"Ortega Gurrola, Alonso"},{"full_name":"Shvartsman, Arik","first_name":"Arik","last_name":"Shvartsman"},{"id":"a9492887-8972-11ed-ae7b-bfae10998254","first_name":"Francesca","last_name":"Barbieri","full_name":"Barbieri, Francesca"},{"full_name":"Toma, Florina-Alexandra","first_name":"Florina-Alexandra","last_name":"Toma","id":"85dd99f2-15b2-11ec-abd3-d1ae4d57f3b5"},{"last_name":"Gorbsky","first_name":"Gary J.","full_name":"Gorbsky, Gary J."},{"last_name":"Horb","first_name":"Marko E.","full_name":"Horb, Marko E."},{"first_name":"Hollis T.","last_name":"Cline","full_name":"Cline, Hollis T."},{"last_name":"Shay","first_name":"Timothy F.","full_name":"Shay, Timothy F."},{"last_name":"Kelley","first_name":"Darcy B.","full_name":"Kelley, Darcy B."},{"full_name":"Yamaguchi, Ayako","first_name":"Ayako","last_name":"Yamaguchi"},{"full_name":"Shein-Idelson, Mark","last_name":"Shein-Idelson","first_name":"Mark"},{"last_name":"Tosches","first_name":"Maria Antonietta","full_name":"Tosches, Maria Antonietta"},{"orcid":"0000-0001-9242-5601","id":"56BE8254-C4F0-11E9-8E45-0B23E6697425","last_name":"Sweeney","first_name":"Lora Beatrice Jaeger","full_name":"Sweeney, Lora Beatrice Jaeger"}],"article_processing_charge":"No","day":"16","month":"02","project":[{"name":"Entwicklung und Funktion der V1 Interneuronen vom Schwimmen zum Laufen während der Metamorphose von Xenopus","grant_number":"FTI21-D-046","_id":"bd73af52-d553-11ed-ba76-912049f0ac7a"},{"name":"Development and Evolution of Tetrapod Motor Circuits","_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae","grant_number":"101041551"}],"oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2024.02.15.580289"}],"citation":{"mla":"Jaeger, Eliza C. B., et al. “Adeno-Associated Viral Tools to Trace Neural Development and Connectivity across Amphibians.” BioRxiv, doi:10.1101/2024.02.15.580289.","short":"E.C.B. Jaeger, D. Vijatovic, A. Deryckere, N. Zorin, A.L. Nguyen, G. Ivanian, J. Woych, R.C. Arnold, A. Ortega Gurrola, A. Shvartsman, F. Barbieri, F.-A. Toma, G.J. Gorbsky, M.E. Horb, H.T. Cline, T.F. Shay, D.B. Kelley, A. Yamaguchi, M. Shein-Idelson, M.A. Tosches, L.B. Sweeney, BioRxiv (n.d.).","chicago":"Jaeger, Eliza C.B., David Vijatovic, Astrid Deryckere, Nikol Zorin, Akemi L. Nguyen, Georgiy Ivanian, Jamie Woych, et al. “Adeno-Associated Viral Tools to Trace Neural Development and Connectivity across Amphibians.” BioRxiv, n.d. https://doi.org/10.1101/2024.02.15.580289.","ama":"Jaeger ECB, Vijatovic D, Deryckere A, et al. Adeno-associated viral tools to trace neural development and connectivity across amphibians. bioRxiv. doi:10.1101/2024.02.15.580289","ista":"Jaeger ECB, Vijatovic D, Deryckere A, Zorin N, Nguyen AL, Ivanian G, Woych J, Arnold RC, Ortega Gurrola A, Shvartsman A, Barbieri F, Toma F-A, Gorbsky GJ, Horb ME, Cline HT, Shay TF, Kelley DB, Yamaguchi A, Shein-Idelson M, Tosches MA, Sweeney LB. Adeno-associated viral tools to trace neural development and connectivity across amphibians. bioRxiv, 10.1101/2024.02.15.580289.","ieee":"E. C. B. Jaeger et al., “Adeno-associated viral tools to trace neural development and connectivity across amphibians,” bioRxiv. .","apa":"Jaeger, E. C. B., Vijatovic, D., Deryckere, A., Zorin, N., Nguyen, A. L., Ivanian, G., … Sweeney, L. B. (n.d.). Adeno-associated viral tools to trace neural development and connectivity across amphibians. bioRxiv. https://doi.org/10.1101/2024.02.15.580289"},"publication":"bioRxiv","language":[{"iso":"eng"}],"date_published":"2024-02-16T00:00:00Z","doi":"10.1101/2024.02.15.580289"},{"abstract":[{"lang":"eng","text":"Vertebrate movement is orchestrated by spinal inter- and motor neurons that, together with sensory and cognitive input, produce dynamic motor behaviors. These behaviors vary from the simple undulatory swimming of fish and larval aquatic species to the highly coordinated running, reaching and grasping of mice, humans and other mammals. This variation raises the fundamental question of how spinal circuits have changed in register with motor behavior. In simple, undulatory fish, exemplified by the lamprey, two broad classes of interneurons shape motor neuron output: ipsilateral-projecting excitatory neurons, and commissural-projecting inhibitory neurons. An additional class of ipsilateral inhibitory neurons is required to generate escape swim behavior in larval zebrafish and tadpoles. In limbed vertebrates, a more complex spinal neuron composition is observed. In this review, we provide evidence that movement elaboration correlates with an increase and specialization of these three basic interneuron types into molecularly, anatomically, and functionally distinct subpopulations. We summarize recent work linking neuron types to movement-pattern generation across fish, amphibians, reptiles, birds and mammals."}],"type":"journal_article","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2023_FrontiersNeuralCircuits_Wilson.pdf","file_size":6667157,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"14729","checksum":"7efd06de284a28e91e97127611a9c3fd","success":1,"date_updated":"2024-01-03T13:33:21Z","date_created":"2024-01-03T13:33:21Z"}],"_id":"13097","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Spinal cords: Symphonies of interneurons across species","status":"public","ddc":["570"],"intvolume":" 17","day":"26","has_accepted_license":"1","article_processing_charge":"Yes","scopus_import":"1","date_published":"2023-04-26T00:00:00Z","publication":"Frontiers in Neural Circuits","citation":{"ama":"Wilson AC, Sweeney LB. Spinal cords: Symphonies of interneurons across species. Frontiers in Neural Circuits. 2023;17. doi:10.3389/fncir.2023.1146449","apa":"Wilson, A. C., & Sweeney, L. B. (2023). Spinal cords: Symphonies of interneurons across species. Frontiers in Neural Circuits. Frontiers. https://doi.org/10.3389/fncir.2023.1146449","ieee":"A. C. Wilson and L. B. Sweeney, “Spinal cords: Symphonies of interneurons across species,” Frontiers in Neural Circuits, vol. 17. Frontiers, 2023.","ista":"Wilson AC, Sweeney LB. 2023. Spinal cords: Symphonies of interneurons across species. Frontiers in Neural Circuits. 17, 1146449.","short":"A.C. Wilson, L.B. Sweeney, Frontiers in Neural Circuits 17 (2023).","mla":"Wilson, Alexia C., and Lora B. Sweeney. “Spinal Cords: Symphonies of Interneurons across Species.” Frontiers in Neural Circuits, vol. 17, 1146449, Frontiers, 2023, doi:10.3389/fncir.2023.1146449.","chicago":"Wilson, Alexia C, and Lora B. Sweeney. “Spinal Cords: Symphonies of Interneurons across Species.” Frontiers in Neural Circuits. Frontiers, 2023. https://doi.org/10.3389/fncir.2023.1146449."},"article_type":"original","file_date_updated":"2024-01-03T13:33:21Z","article_number":"1146449","author":[{"id":"5230e794-15b2-11ec-abd3-e2d5335ebd1d","first_name":"Alexia C","last_name":"Wilson","full_name":"Wilson, Alexia C"},{"id":"56BE8254-C4F0-11E9-8E45-0B23E6697425","orcid":"0000-0001-9242-5601","first_name":"Lora Beatrice Jaeger","last_name":"Sweeney","full_name":"Sweeney, Lora Beatrice Jaeger"}],"date_updated":"2024-01-31T10:15:53Z","date_created":"2023-05-28T22:01:04Z","volume":17,"year":"2023","acknowledgement":"This work was supported by the ERC Starting grant, ERC-2021-STG #101041551.","pmid":1,"publication_status":"published","publisher":"Frontiers","department":[{"_id":"LoSw"}],"month":"04","publication_identifier":{"issn":["1662-5110"]},"doi":"10.3389/fncir.2023.1146449","language":[{"iso":"eng"}],"external_id":{"pmid":["37180760"],"isi":["000984606200001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"isi":1,"quality_controlled":"1","project":[{"_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae","grant_number":"101041551","name":"Development and Evolution of Tetrapod Motor Circuits"}]},{"date_created":"2022-03-24T13:23:09Z","date_updated":"2023-08-03T06:13:14Z","volume":41,"author":[{"full_name":"Emtenani, Shamsi","first_name":"Shamsi","last_name":"Emtenani","id":"49D32318-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6981-6938"},{"full_name":"Martin, Elliot T","last_name":"Martin","first_name":"Elliot T"},{"orcid":"0000-0002-1819-198X","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","last_name":"György","first_name":"Attila","full_name":"György, Attila"},{"full_name":"Bicher, Julia","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Bicher"},{"last_name":"Genger","first_name":"Jakob-Wendelin","full_name":"Genger, Jakob-Wendelin"},{"last_name":"Köcher","first_name":"Thomas","full_name":"Köcher, Thomas"},{"full_name":"Akhmanova, Maria","first_name":"Maria","last_name":"Akhmanova","id":"3425EC26-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1522-3162"},{"id":"6de81d9d-e2f2-11eb-945a-af8bc2a60b26","first_name":"Mariana","last_name":"Pereira Guarda","full_name":"Pereira Guarda, Mariana"},{"first_name":"Marko","last_name":"Roblek","id":"3047D808-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9588-1389","full_name":"Roblek, Marko"},{"first_name":"Andreas","last_name":"Bergthaler","full_name":"Bergthaler, Andreas"},{"full_name":"Hurd, Thomas R","first_name":"Thomas R","last_name":"Hurd"},{"last_name":"Rangan","first_name":"Prashanth","full_name":"Rangan, Prashanth"},{"full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","last_name":"Siekhaus","first_name":"Daria E"}],"publication_status":"published","publisher":"Embo Press","department":[{"_id":"DaSi"},{"_id":"LoSw"}],"acknowledgement":"We thank the DGRC (NIH grant 2P40OD010949-10A1) for plasmids, the BDSC (NIH grant P40OD018537) and the VDRC for fly stocks, FlyBase for essential genomic information, the BDGP in situ database for data (Tomancak et al, 2007), the IST Austria Bioimaging facility for support, the VBC Core Facilities for RNA sequencing and analysis, and C. Guet, C. Navarro, C. Desplan, T. Lecuit, I. Miguel-Aliaga, and Siekhaus group members for comments on the manuscript. The VBCF Metabolomics Facility is funded by the City of Vienna through the Vienna Business Agency. This work was supported by the Marie Curie CIG 334077/IRTIM (DES), Austrian Science Fund (FWF) Lise Meitner Fellowship M2379-B28 (MA and DES), Austrian Science Fund (FWF) grant ASI_FWF01_P29638S (DES), NIH/NIGMS (R01GM111779-06 (PR), RO1GM135628-01 (PR), European Research Council (ERC) grant no. 677006 “CMIL” (AB), and Natural Sciences and Engineering Research Council of Canada\r\n(RGPIN-2019-06766) (TRH). ","year":"2022","file_date_updated":"2022-03-24T13:22:41Z","ec_funded":1,"article_number":"e109049","acknowledged_ssus":[{"_id":"Bio"}],"language":[{"iso":"eng"}],"doi":"10.15252/embj.2021109049","isi":1,"quality_controlled":"1","project":[{"name":"Investigating the role of transporters in invasive migration through junctions","call_identifier":"FP7","grant_number":"334077","_id":"2536F660-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"Modeling epithelial tissue mechanics during cell invasion","_id":"264CBBAC-B435-11E9-9278-68D0E5697425","grant_number":"M02379"},{"grant_number":"P29638","_id":"253B6E48-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Drosophila TNFa´s Funktion in Immunzellen"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000771957000001"]},"month":"03","publication_identifier":{"eissn":["1460-2075"]},"oa_version":"Published Version","file":[{"file_size":4344585,"content_type":"application/pdf","creator":"siekhaus","file_name":"Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosopila.pdf","access_level":"open_access","date_updated":"2022-03-24T13:22:41Z","date_created":"2022-03-24T13:22:41Z","checksum":"dba48580fe0fefaa4c63078d1d2a35df","relation":"main_file","file_id":"10919"}],"ddc":["570"],"title":"Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila","status":"public","intvolume":" 41","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10918","abstract":[{"text":"Cellular metabolism must adapt to changing demands to enable homeostasis. During immune responses or cancer metastasis, cells leading migration into challenging environments require an energy boost, but what controls this capacity is unclear. Here, we study a previously uncharacterized nuclear protein, Atossa (encoded by CG9005), which supports macrophage invasion into the germband of Drosophila by controlling cellular metabolism. First, nuclear Atossa increases mRNA levels of Porthos, a DEAD-box protein, and of two metabolic enzymes, lysine-α-ketoglutarate reductase (LKR/SDH) and NADPH glyoxylate reductase (GR/HPR), thus enhancing mitochondrial bioenergetics. Then Porthos supports ribosome assembly and thereby raises the translational efficiency of a subset of mRNAs, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Mitochondrial respiration measurements, metabolomics, and live imaging indicate that Atossa and Porthos power up OxPhos and energy production to promote the forging of a path into tissues by leading macrophages. Since many crucial physiological responses require increases in mitochondrial energy output, this previously undescribed genetic program may modulate a wide range of cellular behaviors.","lang":"eng"}],"type":"journal_article","date_published":"2022-03-23T00:00:00Z","article_type":"original","publication":"The Embo Journal","citation":{"ama":"Emtenani S, Martin ET, György A, et al. Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila. The Embo Journal. 2022;41. doi:10.15252/embj.2021109049","apa":"Emtenani, S., Martin, E. T., György, A., Bicher, J., Genger, J.-W., Köcher, T., … Siekhaus, D. E. (2022). Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila. The Embo Journal. Embo Press. https://doi.org/10.15252/embj.2021109049","ieee":"S. Emtenani et al., “Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila,” The Embo Journal, vol. 41. Embo Press, 2022.","ista":"Emtenani S, Martin ET, György A, Bicher J, Genger J-W, Köcher T, Akhmanova M, Pereira Guarda M, Roblek M, Bergthaler A, Hurd TR, Rangan P, Siekhaus DE. 2022. Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila. The Embo Journal. 41, e109049.","short":"S. Emtenani, E.T. Martin, A. György, J. Bicher, J.-W. Genger, T. Köcher, M. Akhmanova, M. Pereira Guarda, M. Roblek, A. Bergthaler, T.R. Hurd, P. Rangan, D.E. Siekhaus, The Embo Journal 41 (2022).","mla":"Emtenani, Shamsi, et al. “Macrophage Mitochondrial Bioenergetics and Tissue Invasion Are Boosted by an Atossa-Porthos Axis in Drosophila.” The Embo Journal, vol. 41, e109049, Embo Press, 2022, doi:10.15252/embj.2021109049.","chicago":"Emtenani, Shamsi, Elliot T Martin, Attila György, Julia Bicher, Jakob-Wendelin Genger, Thomas Köcher, Maria Akhmanova, et al. “Macrophage Mitochondrial Bioenergetics and Tissue Invasion Are Boosted by an Atossa-Porthos Axis in Drosophila.” The Embo Journal. Embo Press, 2022. https://doi.org/10.15252/embj.2021109049."},"day":"23","has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","scopus_import":"1"},{"publication_status":"published","publisher":"Public Library of Science","department":[{"_id":"EM-Fac"},{"_id":"LoSw"},{"_id":"DaSi"}],"acknowledgement":"We thank R. Cagan, A. Whitworth and J. Nagpal for fly lines and advice, S. Herlitze for provision of a tissue culture illuminator, and Verian Bader for help with statistical analysis.","year":"2021","date_created":"2021-05-02T22:01:29Z","date_updated":"2023-08-08T13:17:47Z","volume":17,"author":[{"orcid":"0000-0002-5409-8571","id":"2A9DB292-F248-11E8-B48F-1D18A9856A87","last_name":"Inglés Prieto","first_name":"Álvaro","full_name":"Inglés Prieto, Álvaro"},{"full_name":"Furthmann, Nikolas","first_name":"Nikolas","last_name":"Furthmann"},{"first_name":"Samuel H.","last_name":"Crossman","full_name":"Crossman, Samuel H."},{"full_name":"Tichy, Alexandra Madelaine","last_name":"Tichy","first_name":"Alexandra Madelaine"},{"full_name":"Hoyer, Nina","last_name":"Hoyer","first_name":"Nina"},{"first_name":"Meike","last_name":"Petersen","full_name":"Petersen, Meike"},{"full_name":"Zheden, Vanessa","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","first_name":"Vanessa","last_name":"Zheden"},{"first_name":"Julia","last_name":"Bicher","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","full_name":"Bicher, Julia"},{"full_name":"Gschaider-Reichhart, Eva","last_name":"Gschaider-Reichhart","first_name":"Eva","orcid":"0000-0002-7218-7738","id":"3FEE232A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Attila","last_name":"György","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X","full_name":"György, Attila"},{"full_name":"Siekhaus, Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","first_name":"Daria E","last_name":"Siekhaus"},{"full_name":"Soba, Peter","first_name":"Peter","last_name":"Soba"},{"last_name":"Winklhofer","first_name":"Konstanze F.","full_name":"Winklhofer, Konstanze F."},{"last_name":"Janovjak","first_name":"Harald L","orcid":"0000-0002-8023-9315","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","full_name":"Janovjak, Harald L"}],"file_date_updated":"2021-05-04T09:05:27Z","quality_controlled":"1","isi":1,"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000640606700001"]},"language":[{"iso":"eng"}],"doi":"10.1371/journal.pgen.1009479","month":"04","publication_identifier":{"eissn":["15537404"]},"title":"Optogenetic delivery of trophic signals in a genetic model of Parkinson's disease","ddc":["570"],"status":"public","intvolume":" 17","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"9363","file":[{"file_name":"2021_PLOS_Ingles-Prieto.pdf","access_level":"open_access","creator":"kschuh","content_type":"application/pdf","file_size":3072764,"file_id":"9369","relation":"main_file","date_updated":"2021-05-04T09:05:27Z","date_created":"2021-05-04T09:05:27Z","success":1,"checksum":"82a74668f863e8dfb22fdd4f845c92ce"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"text":"Optogenetics has been harnessed to shed new mechanistic light on current and future therapeutic strategies. This has been to date achieved by the regulation of ion flow and electrical signals in neuronal cells and neural circuits that are known to be affected by disease. In contrast, the optogenetic delivery of trophic biochemical signals, which support cell survival and are implicated in degenerative disorders, has never been demonstrated in an animal model of disease. Here, we reengineered the human and Drosophila melanogaster REarranged during Transfection (hRET and dRET) receptors to be activated by light, creating one-component optogenetic tools termed Opto-hRET and Opto-dRET. Upon blue light stimulation, these receptors robustly induced the MAPK/ERK proliferative signaling pathway in cultured cells. In PINK1B9 flies that exhibit loss of PTEN-induced putative kinase 1 (PINK1), a kinase associated with familial Parkinson’s disease (PD), light activation of Opto-dRET suppressed mitochondrial defects, tissue degeneration and behavioral deficits. In human cells with PINK1 loss-of-function, mitochondrial fragmentation was rescued using Opto-dRET via the PI3K/NF-кB pathway. Our results demonstrate that a light-activated receptor can ameliorate disease hallmarks in a genetic model of PD. The optogenetic delivery of trophic signals is cell type-specific and reversible and thus has the potential to inspire novel strategies towards a spatio-temporal regulation of tissue repair.","lang":"eng"}],"issue":"4","page":"e1009479","publication":"PLoS genetics","citation":{"ama":"Inglés Prieto Á, Furthmann N, Crossman SH, et al. Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease. PLoS genetics. 2021;17(4):e1009479. doi:10.1371/journal.pgen.1009479","ieee":"Á. Inglés Prieto et al., “Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease,” PLoS genetics, vol. 17, no. 4. Public Library of Science, p. e1009479, 2021.","apa":"Inglés Prieto, Á., Furthmann, N., Crossman, S. H., Tichy, A. M., Hoyer, N., Petersen, M., … Janovjak, H. L. (2021). Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1009479","ista":"Inglés Prieto Á, Furthmann N, Crossman SH, Tichy AM, Hoyer N, Petersen M, Zheden V, Bicher J, Gschaider-Reichhart E, György A, Siekhaus DE, Soba P, Winklhofer KF, Janovjak HL. 2021. Optogenetic delivery of trophic signals in a genetic model of Parkinson’s disease. PLoS genetics. 17(4), e1009479.","short":"Á. Inglés Prieto, N. Furthmann, S.H. Crossman, A.M. Tichy, N. Hoyer, M. Petersen, V. Zheden, J. Bicher, E. Gschaider-Reichhart, A. György, D.E. Siekhaus, P. Soba, K.F. Winklhofer, H.L. Janovjak, PLoS Genetics 17 (2021) e1009479.","mla":"Inglés Prieto, Álvaro, et al. “Optogenetic Delivery of Trophic Signals in a Genetic Model of Parkinson’s Disease.” PLoS Genetics, vol. 17, no. 4, Public Library of Science, 2021, p. e1009479, doi:10.1371/journal.pgen.1009479.","chicago":"Inglés Prieto, Álvaro, Nikolas Furthmann, Samuel H. Crossman, Alexandra Madelaine Tichy, Nina Hoyer, Meike Petersen, Vanessa Zheden, et al. “Optogenetic Delivery of Trophic Signals in a Genetic Model of Parkinson’s Disease.” PLoS Genetics. Public Library of Science, 2021. https://doi.org/10.1371/journal.pgen.1009479."},"date_published":"2021-04-01T00:00:00Z","scopus_import":"1","day":"01","has_accepted_license":"1","article_processing_charge":"No"},{"ec_funded":1,"file_date_updated":"2021-06-28T14:06:24Z","article_number":"109274","related_material":{"link":[{"url":"https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/","description":"News on IST Homepage","relation":"press_release"}]},"author":[{"id":"475990FE-F248-11E8-B48F-1D18A9856A87","last_name":"Contreras","first_name":"Ximena","full_name":"Contreras, Ximena"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","first_name":"Nicole","last_name":"Amberg","full_name":"Amberg, Nicole"},{"first_name":"Amarbayasgalan","last_name":"Davaatseren","id":"70ADC922-B424-11E9-99E3-BA18E6697425","full_name":"Davaatseren, Amarbayasgalan"},{"first_name":"Andi H","last_name":"Hansen","id":"38853E16-F248-11E8-B48F-1D18A9856A87","full_name":"Hansen, Andi H"},{"full_name":"Sonntag, Johanna","last_name":"Sonntag","first_name":"Johanna","id":"32FE7D7C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Andersen, Lill","first_name":"Lill","last_name":"Andersen"},{"full_name":"Bernthaler, Tina","last_name":"Bernthaler","first_name":"Tina"},{"last_name":"Streicher","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen"},{"id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","last_name":"Heger","first_name":"Anna-Magdalena","full_name":"Heger, Anna-Magdalena"},{"first_name":"Randy L.","last_name":"Johnson","full_name":"Johnson, Randy L."},{"last_name":"Schwarz","first_name":"Lindsay A.","full_name":"Schwarz, Lindsay A."},{"full_name":"Luo, Liqun","first_name":"Liqun","last_name":"Luo"},{"full_name":"Rülicke, Thomas","last_name":"Rülicke","first_name":"Thomas"},{"full_name":"Hippenmeyer, Simon","first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061"}],"volume":35,"date_created":"2021-06-27T22:01:48Z","date_updated":"2023-08-10T13:55:00Z","year":"2021","acknowledgement":"We thank the Bioimaging, Life Science, and Pre-Clinical Facilities at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain, M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance; R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of the Hippenmeyer lab for discussion. This work was supported by National Institutes of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This work also received support from IST Austria institutional funds , FWF SFB F78 to S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 725780 LinPro ) to S.H.","publisher":"Cell Press","department":[{"_id":"SiHi"},{"_id":"LoSw"},{"_id":"PreCl"}],"publication_status":"published","publication_identifier":{"eissn":["22111247"]},"month":"06","doi":"10.1016/j.celrep.2021.109274","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"}],"oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"external_id":{"isi":["000664463600016"]},"project":[{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration"},{"_id":"25D61E48-B435-11E9-9278-68D0E5697425","grant_number":"618444","name":"Molecular Mechanisms of Cerebral Cortex Development","call_identifier":"FP7"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020"}],"quality_controlled":"1","isi":1,"issue":"12","abstract":[{"text":"Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice with single-cell resolution. MADM applications include the analysis of lineage, single-cell morphology and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous gene functions in vivo in health and disease. Yet, MADM can only be applied to <25% of all mouse genes on select chromosomes to date. To overcome this limitation, we generate transgenic mice with knocked-in MADM cassettes near the centromeres of all 19 autosomes and validate their use across organs. With this resource, >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic analysis. Beyond a proof of principle, we apply our MADM library to systematically trace sister chromatid segregation in distinct mitotic cell lineages. We find striking chromosome-specific biases in segregation patterns, reflecting a putative mechanism for the asymmetric segregation of genetic determinants in somatic stem cell division.","lang":"eng"}],"type":"journal_article","file":[{"creator":"asandaue","file_size":7653149,"content_type":"application/pdf","file_name":"2021_CellReports_Contreras.pdf","access_level":"open_access","date_created":"2021-06-28T14:06:24Z","date_updated":"2021-06-28T14:06:24Z","success":1,"checksum":"d49520fdcbbb5c2f883bddb67cee5d77","file_id":"9613","relation":"main_file"}],"oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"9603","intvolume":" 35","status":"public","ddc":["570"],"title":"A genome-wide library of MADM mice for single-cell genetic mosaic analysis","has_accepted_license":"1","article_processing_charge":"No","day":"22","scopus_import":"1","date_published":"2021-06-22T00:00:00Z","citation":{"mla":"Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports, vol. 35, no. 12, 109274, Cell Press, 2021, doi:10.1016/j.celrep.2021.109274.","short":"X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen, T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo, T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).","chicago":"Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen, Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports. Cell Press, 2021. https://doi.org/10.1016/j.celrep.2021.109274.","ama":"Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 2021;35(12). doi:10.1016/j.celrep.2021.109274","ista":"Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. 35(12), 109274.","apa":"Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen, L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell genetic mosaic analysis. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2021.109274","ieee":"X. Contreras et al., “A genome-wide library of MADM mice for single-cell genetic mosaic analysis,” Cell Reports, vol. 35, no. 12. Cell Press, 2021."},"publication":"Cell Reports","article_type":"original"},{"external_id":{"pmid":["32858144"],"isi":["000595588700008"]},"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"isi":1,"quality_controlled":"1","doi":"10.1016/j.neuroscience.2020.08.011","language":[{"iso":"eng"}],"publication_identifier":{"issn":["0306-4522"]},"month":"12","pmid":1,"acknowledgement":"This work was made possible by the generous support of Project ALS. Imaging and related analyses were facilitated by The Waitt Advanced Biophotonics Center Core at the Salk Institute, supported by grants from NIH-NCI CCSG (P30 014195) and NINDS Neuroscience Center (NS072031). The authors would like to additionally thank Drs. Jane Dodd, Robert Brownstone, and Laskaro Zagoraiou for helpful comments on the manuscript. This manuscript is dedicated to Tom Jessell, an inspirational scientist, friend and mentor.","year":"2020","publisher":"Elsevier","department":[{"_id":"LoSw"}],"publication_status":"published","author":[{"last_name":"Salamatina","first_name":"Alina","full_name":"Salamatina, Alina"},{"full_name":"Yang, Jerry H","last_name":"Yang","first_name":"Jerry H"},{"full_name":"Brenner-Morton, Susan","first_name":"Susan","last_name":"Brenner-Morton"},{"last_name":"Bikoff","first_name":"Jay B ","full_name":"Bikoff, Jay B "},{"last_name":"Fang","first_name":"Linjing","full_name":"Fang, Linjing"},{"full_name":"Kintner, Christopher R","last_name":"Kintner","first_name":"Christopher R"},{"first_name":"Thomas M","last_name":"Jessell","full_name":"Jessell, Thomas M"},{"last_name":"Sweeney","first_name":"Lora Beatrice Jaeger","orcid":"0000-0001-9242-5601","id":"56BE8254-C4F0-11E9-8E45-0B23E6697425","full_name":"Sweeney, Lora Beatrice Jaeger"}],"volume":450,"date_created":"2020-12-03T11:47:31Z","date_updated":"2024-01-31T10:15:34Z","file_date_updated":"2020-12-03T11:45:26Z","citation":{"chicago":"Salamatina, Alina, Jerry H Yang, Susan Brenner-Morton, Jay B Bikoff, Linjing Fang, Christopher R Kintner, Thomas M Jessell, and Lora B. Sweeney. “Differential Loss of Spinal Interneurons in a Mouse Model of ALS.” Neuroscience. Elsevier, 2020. https://doi.org/10.1016/j.neuroscience.2020.08.011.","mla":"Salamatina, Alina, et al. “Differential Loss of Spinal Interneurons in a Mouse Model of ALS.” Neuroscience, vol. 450, Elsevier, 2020, pp. 81–95, doi:10.1016/j.neuroscience.2020.08.011.","short":"A. Salamatina, J.H. Yang, S. Brenner-Morton, J.B. Bikoff, L. Fang, C.R. Kintner, T.M. Jessell, L.B. Sweeney, Neuroscience 450 (2020) 81–95.","ista":"Salamatina A, Yang JH, Brenner-Morton S, Bikoff JB, Fang L, Kintner CR, Jessell TM, Sweeney LB. 2020. Differential loss of spinal interneurons in a mouse model of ALS. Neuroscience. 450, 81–95.","apa":"Salamatina, A., Yang, J. H., Brenner-Morton, S., Bikoff, J. B., Fang, L., Kintner, C. R., … Sweeney, L. B. (2020). Differential loss of spinal interneurons in a mouse model of ALS. Neuroscience. Elsevier. https://doi.org/10.1016/j.neuroscience.2020.08.011","ieee":"A. Salamatina et al., “Differential loss of spinal interneurons in a mouse model of ALS,” Neuroscience, vol. 450. Elsevier, pp. 81–95, 2020.","ama":"Salamatina A, Yang JH, Brenner-Morton S, et al. Differential loss of spinal interneurons in a mouse model of ALS. Neuroscience. 2020;450:81-95. doi:10.1016/j.neuroscience.2020.08.011"},"publication":"Neuroscience","page":"81-95","article_type":"original","date_published":"2020-12-01T00:00:00Z","scopus_import":"1","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","day":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"8914","intvolume":" 450","title":"Differential loss of spinal interneurons in a mouse model of ALS","ddc":["570"],"status":"public","oa_version":"Published Version","file":[{"success":1,"checksum":"da7413c819e079720669c82451b49294","date_updated":"2020-12-03T11:45:26Z","date_created":"2020-12-03T11:45:26Z","file_id":"8915","relation":"main_file","creator":"dernst","file_size":4071247,"content_type":"application/pdf","access_level":"open_access","file_name":"2020_Neuroscience_Salamatina.pdf"}],"type":"journal_article","abstract":[{"text":"Amyotrophic lateral sclerosis (ALS) leads to a loss of specific motor neuron populations in the spinal cord and cortex. Emerging evidence suggests that interneurons may also be affected, but a detailed characterization of interneuron loss and its potential impacts on motor neuron loss and disease progression is lacking. To examine this issue, the fate of V1 inhibitory neurons during ALS was assessed in the ventral spinal cord using the SODG93A mouse model. The V1 population makes up ∼30% of all ventral inhibitory neurons, ∼50% of direct inhibitory synaptic contacts onto motor neuron cell bodies, and is thought to play a key role in modulating motor output, in part through recurrent and reciprocal inhibitory circuits. We find that approximately half of V1 inhibitory neurons are lost in SODG93A mice at late disease stages, but that this loss is delayed relative to the loss of motor neurons and V2a excitatory neurons. We further identify V1 subpopulations based on transcription factor expression that are differentially susceptible to degeneration in SODG93A mice. At an early disease stage, we show that V1 synaptic contacts with motor neuron cell bodies increase, suggesting an upregulation of inhibition before V1 neurons are lost in substantial numbers. These data support a model in which progressive changes in V1 synaptic contacts early in disease, and in select V1 subpopulations at later stages, represent a compensatory upregulation and then deleterious breakdown of specific interneuron circuits within the spinal cord.","lang":"eng"}]}]