Preformation and epigenesis converge to specify primordial germ cell fate in the early Drosophila embryo

Colonnetta, Megan M; Goyal, Yogesh; Johnson, Heath E.; Syal, Sapna; Schedl, Paul; Deshpande, Girish

doi:10.1371/journal.pgen.1010002

Cited by 13 publications

(13 citation statements)

References 80 publications

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“…The failure to incorporate the full complement of germline determinants is responsible at least in part for the PGC phenotypes observed in the zld and clamp RNA knockdowns. Consistent with this conclusion, similar PGC phenotypes are observed in gcl mutants and in mutants in components of the BMP signaling pathway (Colonnetta et al, 2021b;Colonnetta et al, 2022). In both of these cases, germline determinants are not efficiently captured by the cellularizing PGCs.…”

Section: Discussionmentioning

confidence: 57%

“…In one model, one or more genes expressed during the minor wave could be important in directing the process of PGC cellularization. This is a plausible mechanism as previous studies have shown that PGC formation and proper specification in early embryos depends upon zygotic activity of the BMP pathway (Colonnetta et al, 2022). For example, when dpp expression is inhibited by zygotic RNAi knockdown, germline determinants like gcl and pgc mRNAs, are not fully captured by the PGCs when they cellularize.…”

Section: Discussionmentioning

confidence: 90%

“…However, recent studies have shown that the proper specification of PGC identity in flies is not exclusively determined by preformation-based mechanism. Instead, it also depends upon extrinsic somatic signals from the BMP pathway (Bone morphogenetic pathway) ligand Dpp (Decapentaplegi c ) which is expressed in the early embryo (Colonnetta et al, 2022). For these reasons, we wondered whether the chromatin factors that set the stage for the major wave of ZGA in NC14 also impact the process of PGC specification in early blastoderm embryos.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Deshpande

Colonnetta

Schedl

2022

Preprint

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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 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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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Deshpande

Colonnetta

Schedl

2022

Preprint

Self Cite

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“…The existence of a shared genetic identity in metazoan spermatocytes can be regarded as a ramification of an ancestral multipotency program already present in germ line precursor cells 54 . Indeed, even in species with divergent germ line segregation strategies, conserved functional interactions at the post-translational level are required for primordial germ cell specification 55,56 . The observation that metazoan chromosomes have deeply conserved gene linkages, some stretching as far back as unicellular organisms, provides a plausible mechanistic basis for the persistence of ancient transcriptional programs 57 .…”

Section: Discussionmentioning

confidence: 99%

The conserved genetic program of male germ cells uncovers ancient regulators of human spermatogenesis

Correia

Almeida

Wyrwoll

et al. 2022

Preprint

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Germ cells provide the cellular basis for sexual reproduction in multicellular animals. In males, germ cells differentiate into sperm, one of the most morphologically diverse eukaryotic cell types. Owing both to this remarkable diversity and to the rapid evolution of reproduction-related genes, the transcriptional program of male germ cells is widely regarded as divergent across species1,2. However, the possibility that these cells retain a distinctive evolutionarily-conserved genetic basis remains largely unexplored. Here we show, using phylostratigraphy, that the complex male germ cell transcriptome has an old evolutionary origin shared between vertebrate and invertebrate species. Through network analysis of the human, mouse and fruit fly meiotic transcriptome, we establish that old genes serve as a genetic scaffold from which complexity has evolved, and identify a core set of 79 ancient functional interactions at the heart of male germ cell identity. By silencing a cohort of 920 candidate genes likely to affect the acquisition and maintenance of this identity, we uncover 164 previously unknown spermatogenesis genes. Integrating this information with whole-exome sequencing data from azoospermic men reveals three novel genetic causes of human male infertility associated with germ cell defects shared across more than 600 million years of evolution. Our results demonstrate the central role of old genes in germ cell function and illustrate how comparative biology can be an important tool in medical genetics. We anticipate that our open-access and easily-adaptable interdisciplinary research platform will be harnessed in the context of other cell types and diseases.

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“…However, recent studies have shown that the proper specification of PGC identity in flies is not exclusively determined by preformation-based mechanism. Instead, it also depends upon extrinsic somatic signals from the BMP pathway (bone morphogenetic protein pathway) ligand Dpp (Decapentaplegi c ) which is expressed in the early embryo ( Colonnetta et al, 2022 ). For these reasons, we wondered whether the chromatin factors that set the stage for the major wave of ZGA in NC14 also impact the process of PGC specification in early blastoderm embryos.…”

Section: Introductionmentioning

confidence: 99%

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

Colonnetta

Schedl

Deshpande

2023

eLife

Self Cite

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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.

show abstract

Preformation and epigenesis converge to specify primordial germ cell fate in the early Drosophila embryo

Cited by 13 publications

References 80 publications

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

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

The conserved genetic program of male germ cells uncovers ancient regulators of human spermatogenesis

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

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