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      Germline/soma distinction in Drosophila embryos requires regulators of zygotic genome activation

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          Abstract

          In Drosophila melanogaster embryos, somatic versus germline identity is the first cell fate decision. Zygotic genome activation (ZGA) orchestrates regionalized gene expression, imparting specific identity on somatic cells. ZGA begins with a minor wave that commences at nuclear cycle (NC)8 under the guidance of chromatin accessibility factors (Zelda, CLAMP, GAF), followed by the major wave during NC14. By contrast, primordial germ cell (PGC) specification requires maternally deposited and posteriorly anchored germline determinants. This is accomplished by a centrosome coordinated release and sequestration of germ plasm during the precocious cellularization of PGCs in NC10. Here, we report a novel requirement for Zelda and CLAMP during the establishment of the germline/soma distinction. When their activity is compromised, PGC determinants are not properly sequestered, and specification is disrupted. Conversely, the spreading of PGC determinants from the posterior pole adversely influences transcription in the neighboring somatic nuclei. These reciprocal aberrations can be correlated with defects in centrosome duplication/separation that are known to induce inappropriate transmission of the germ plasm. Interestingly, consistent with the ability of bone morphogenetic protein (BMP) signaling to influence specification of embryonic PGCs, reduction in the transcript levels of a BMP family ligand, decapentaplegic ( dpp), is exacerbated at the posterior pole.

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          Mechanisms of germ cell specification across the metazoans: epigenesis and preformation.

          Germ cells play a unique role in gamete production, heredity and evolution. Therefore, to understand the mechanisms that specify germ cells is a central challenge in developmental and evolutionary biology. Data from model organisms show that germ cells can be specified either by maternally inherited determinants (preformation) or by inductive signals (epigenesis). Here we review existing data on 28 metazoan phyla, which indicate that although preformation is seen in most model organisms, it is actually the less prevalent mode of germ cell specification, and that epigenetic germ cell specification may be ancestral to the Metazoa.
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            Chromatin Architecture Emerges during Zygotic Genome Activation Independent of Transcription.

            Chromatin architecture is fundamental in regulating gene expression. To investigate when spatial genome organization is first established during development, we examined chromatin conformation during Drosophila embryogenesis and observed the emergence of chromatin architecture within a tight time window that coincides with the onset of transcription activation in the zygote. Prior to zygotic genome activation, the genome is mostly unstructured. Early expressed genes serve as nucleation sites for topologically associating domain (TAD) boundaries. Activation of gene expression coincides with the establishment of TADs throughout the genome and co-localization of housekeeping gene clusters, which remain stable in subsequent stages of development. However, the appearance of TAD boundaries is independent of transcription and requires the transcription factor Zelda for locus-specific TAD boundary insulation. These results offer insight into when spatial organization of the genome emerges and identify a key factor that helps trigger this architecture.
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              The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila

              In all animals, the initial events of embryogenesis are controlled by maternal gene products that are deposited into the developing oocyte. At some point after fertilization, control of embryogenesis is transferred to the zygotic genome in a process called the maternal to zygotic transition (MZT). During this time many maternal RNAs are degraded and transcription of zygotic RNAs ensues1. A longstanding question has been, what factors regulate these events? The recent findings that microRNAs2,3 and Smaugs4 mediate maternal transcript degradation have shed new light on this aspect of the problem. However, the transcription factor(s) that activate the zygotic genome remain elusive. The discovery that many of the early transcribed genes in Drosophila share a cis-regulatory heptamer motif, CAGGTAG and related sequences5,6, collectively referred to as TAGteam sites5 brought up the possibility that a dedicated transcription factor could interact with these sites to activate transcription. Here we report that the zinc-finger protein, Zelda (Zld; Zinc-finger early Drosophila activator), binds specifically to these sites, and is capable of activating transcription in transient transfection assays. Mutant embryos lacking zld are defective in cellular blastoderm formation, and fail to activate many genes essential for cellularization, sex determination, and pattern formation. Global expression profiling confirmed that Zld plays a key role in the activation of the early zygotic genome, and suggests that Zld may also regulate maternal RNA degradation during the MZT.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                04 January 2023
                2023
                : 12
                : e78188
                Affiliations
                [1 ] Department of Molecular Biology, Princeton University ( https://ror.org/00hx57361) Princeton United States
                Max Planck Institute for Biology Tübingen ( https://ror.org/0243gzr89) Germany
                Max Planck Institute for Biology Tübingen ( https://ror.org/0243gzr89) Germany
                Max Planck Institute for Biology Tübingen ( https://ror.org/0243gzr89) Germany
                Max Planck Institute for Biology Tübingen ( https://ror.org/0243gzr89) Germany
                Author information
                https://orcid.org/0000-0001-5685-1670
                https://orcid.org/0000-0002-5200-7090
                Article
                78188
                10.7554/eLife.78188
                9812407
                36598809
                e8cf228b-237d-4912-bea9-76067662b816
                © 2023, Colonnetta et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 25 February 2022
                : 23 December 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: GM126975
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: HD093913
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Developmental Biology
                Stem Cells and Regenerative Medicine
                Custom metadata
                Components of zygotic genome activation, Zelda and CLAMP, contribute to the proper specification of primordial germ cells in Drosophila embryos.

                Life sciences
                zga,germ cells,drosophila melanogaster,embryonic development,stem cells,d. melanogaster
                Life sciences
                zga, germ cells, drosophila melanogaster, embryonic development, stem cells, d. melanogaster

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