A conserved node in the regulation of Vasa between an induced and an inherited program of primordial germ cell specification

Perillo, Margherita; Swartz, S. Zachary; Wessel, Gary M.

doi:10.1016/j.ydbio.2021.11.007

Cited by 17 publications

(20 citation statements)

References 24 publications

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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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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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“…A scrambled MASO sequence was used as control. For each knock out experiment, three Cas9 guide RNAs (gRNAs; 150 ng/μl of each gRNA) were used to target genomic DNA as previously described (Perillo et al, 2022). gRNAs (Synthego) were mixed with 750 ng/μl of Cas9 mRNA; control larvae were injected with Cas9 mRNA only.…”

Section: Perturbation Experiments With Maso Injection and Crispr Cas9mentioning

confidence: 99%

“…Figures were made with Adobe Illustrator. EdU incorporation and pharmacological perturbations 5-ethynyl-2-deoxyuridine (EdU) pulse labeling was performed with the Click-IT EdU imaging kit (Life Technologies; Cat#:C10340) as described in (Perillo et al, 2022). A final concentration of 10 mM EdU in sea water for 30 min was used.…”

Section: Perturbation Experiments With Maso Injection and Crispr Cas9mentioning

confidence: 99%

Molecular mechanisms of tubulogenesis revealed in the sea star hydro-vascular organ

Perillo

Swartz

Pieplow

et al. 2022

Preprint

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A fundamental goal in the organogenesis field is to understand how cells organize into tubular shapes. Toward this aim, we have established the hydro-vascular organ in the sea star Patiria miniata as a model for tubulogenesis. In this animal, bilateral tubes grow out from the tip of the developing gut, and precisely extend to specific sites in the larva. This growth requires cell migration coupled with mitosis in distinct zones. Cell proliferation requires FGF signaling, whereas the three-dimensional orientation of the organ depends on Wnt signaling. Specification and maintenance of tube cell fate requires Delta/Notch signaling. Moreover, we identify target genes of the FGF pathway that contribute to tube morphology, revealing molecular mechanisms for tube outgrowth. Finally, we report that FGF activates the Six1/2 transcription factor, which serves as an evolutionarily ancient regulator of branching morphogenesis. This study uncovers novel mechanisms of tubulogenesis in vivo and we propose that cellular dynamics in the sea star hydro-vascular organ represents a key comparison for understanding the evolution of vertebrate organs.

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“…This is a distinct strategy of cellspecific germ cell factor accumulation in which expression is spread broadly then cleared from cells to yield highly localized expression. In the sea star, Vasa protein is also under strict control through selective post-translational degradation by Gustavus, an E3 ligase [46]. In the future, investigating how Nanos protein localization is regulated will inform us whether these transcripts are also under distinct regulation at the protein level.…”

Section: Inductive Signals In Sea Star Germ Cell Specificationmentioning

confidence: 99%

Distinct mechanisms of germ cell factor regulation for an inductive germ cell fate

Foster

Oulhen

Fresques

et al. 2022

Preprint

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Specification of primordial germ cells (PGCs), the lineage which gives rise to eggs and sperm, is essential for sexually reproducing organisms. The mechanism by which animals specify their PGCs generally falls into two categories: inherited or inductive. The inductive mechanism, used by mammals, relies on cell signaling interactions to direct a subset of embryonic cells to a germ cell fate. Previous work suggested that sea star embryos, which develop in simple culture and are markedly transparent, also use inductive mechanisms to specify their germline. The germ cell factors Nanos and Vasa become restricted during early development into a localized region of cells within the posterior enterocoel (PE), the presumptive germline. Nodal signaling was observed to negatively regulate Vasa and Nanos mRNAs outside of the PE and restrict the germline to the PE. Here we employed single cell RNA sequencing to identify the transcriptional program of germ cells and their changes during development. We never see Nodal pathway members within Nanos/Vasa positive cells in the region known to give rise to the PE, and instead see members of the Wnt-signaling pathway and the FoxY family of transcription factors. We learned that Wnt and Delta/Notch signaling enhances expression of both Nanos and Vasa, whereas a test of cell interactions reveals that Nanos and Vasa are regulated distinctly. This work provides insights into the sequence of events that leads to PGC specification and enables deeper mechanistic studies in a tractable in vivo model.

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A conserved node in the regulation of Vasa between an induced and an inherited program of primordial germ cell specification

Cited by 17 publications

References 24 publications

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

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

Molecular mechanisms of tubulogenesis revealed in the sea star hydro-vascular organ

Distinct mechanisms of germ cell factor regulation for an inductive germ cell fate

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