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Regulators of male and female sexual development are critical for the transmission of a malaria parasite
Wellcome Sanger Institute, Hinxton, United Kingdom.
Wellcome Sanger Institute, Hinxton, United Kingdom; Francis Crick Institute, 1 Midland Road, London, United Kingdom.
Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Wellcome Sanger Institute, Hinxton, United Kingdom.ORCID iD: 0000-0003-2863-4112
Wellcome Sanger Institute, Hinxton, United Kingdom; MIVEGEC, University of Montpellier, IRD, CNRS, Montpellier, France.
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2023 (English)In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 31, no 2, p. 305-319.e10Article in journal (Refereed) Published
Abstract [en]

Malaria transmission to mosquitoes requires a developmental switch in asexually dividing blood-stage parasites to sexual reproduction. In Plasmodium berghei, the transcription factor AP2-G is required and sufficient for this switch, but how a particular sex is determined in a haploid parasite remains unknown. Using a global screen of barcoded mutants, we here identify genes essential for the formation of either male or female sexual forms and validate their importance for transmission. High-resolution single-cell transcriptomics of ten mutant parasites portrays the developmental bifurcation and reveals a regulatory cascade of putative gene functions in the determination and subsequent differentiation of each sex. A male-determining gene with a LOTUS/OST-HTH domain as well as the protein interactors of a female-determining zinc-finger protein indicate that germ-granule-like ribonucleoprotein complexes complement transcriptional processes in the regulation of both male and female development of a malaria parasite.

Place, publisher, year, edition, pages
Cell Press, 2023. Vol. 31, no 2, p. 305-319.e10
Keywords [en]
development, differentiation, malaria, Plasmodium, sex determination, sex ratio, single cell analysis, transmission
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-212243DOI: 10.1016/j.chom.2022.12.011ISI: 000964163800001PubMedID: 36634679Scopus ID: 2-s2.0-85147451944OAI: oai:DiVA.org:umu-212243DiVA, id: diva2:1783358
Funder
Wellcome trust, 206194/Z/17/ZKnut and Alice Wallenberg FoundationEU, European Research Council, 788516Wellcome trust, 083811Wellcome trust, 104111Wellcome trust, 107046Wellcome trust, 202600/Z/ 16/ZAvailable from: 2023-07-20 Created: 2023-07-20 Last updated: 2023-07-20Bibliographically approved

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Bushell, EllenHunziker, MirjamPandey, VikashSayers, ClaireBillker, Oliver

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Bushell, EllenHunziker, MirjamPandey, VikashSayers, ClaireBillker, Oliver
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Molecular Infection Medicine Sweden (MIMS)Department of Molecular Biology (Faculty of Medicine)Department of Molecular Biology (Faculty of Science and Technology)
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Cell Host and Microbe
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