DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells

Chen, Hsu-Hsin; Welling, Maaike; Bloch, Donald B.; Muñoz, Javier; Mientjes, Edwin; Chen, Xinjie; Tramp, Cody Alexander; Wu, Jie; Yabuuchi, Akiko; Chou, Yu-Fen; Buecker, Christa; Krainer, Adrian R.; Willemsen, Rob; Heck, Albert J. R.; Geijsen, Niels

doi:10.1016/j.stemcr.2014.09.003

Cited by 85 publications

(92 citation statements)

References 44 publications

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“…DAZL marker is conserved in all vertebrates, and it has been associated with normal development to germ cells, besides being related to spermatogonial differentiation or in the meiosis beginning. In mice, the non‐expression of this gene results in infertility in both sexes (Chen et al, , ).…”

Section: Discussionmentioning

confidence: 99%

The timeline development of female canine germ cells

Souza

Ramos

Cury

et al. 2019

Reprod Domestic Animals

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During the sex differentiation, the primordial germ cells (PGCs) pass through a differentiation, becoming spermatogonial cells in males and oocytes in females. In this phase, there is difference in gene expression and differentiation potency between males and females. Specific cell markers have been essential in the PGC meiosis beginning and become oocyte cells. However, there are few studies about germline in domestic animals. The domestic dog (Canis lupus familiaris) is an interesting animal model to be used in the investigation about the mammal development because it has several biochemical and physiological similarities to humans. In addition, some additional investigations about dogs may contribute to a better understanding of the biology and genetic components, improving clinical veterinary and zoological sciences. Here, we elucidated by immunofluorescence and quantitative reverse transcriptase‐polymerase chain reaction (RT‐qPCR), the dynamics of the expression of pluripotent (POU5F1 and NANOG) and germline (DDX4, DAZL and DPPA3) markers that are very important in the development of female canine germ cells during 35–50 days post‐fertilization (dpf). The female canine germ cells were positive for pluripotent markers during middle developmental period. The number of DDX4, DAZL and DPPA3 cells increased along the germ cell maturation from 45 to 50 dpf. We provided an expression analysis of the pluripotent and germline markers in paraffin sections using the middle and later periods in female canine germ cells. The results can contribute the understanding about the timeline of each marker along the maturation of female canine germ cells. These results have a great significance to demonstrate the germ cell profile changes because it may allow the development of protocols about in vitro germ cell derivation.

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Section: Discussionmentioning

confidence: 99%

The timeline development of female canine germ cells

Souza

Ramos

Cury

et al. 2019

Reprod Domestic Animals

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“…The more recent discovery of teratomas in the C. elegans germline offers new perspectives into the molecular mechanisms regulating totipotency [113][114][115][116]. In both mouse and C. elegans, inactivation of the translational repressors has revealed important roles in maintaining germline totipotency, and in C. elegans, their absence alone is sufficient to form teratomas [113,116,117]. By contrast, while Drosophila RBPs play a conserved role in translational control of germ stem cell differentiation (reviewed in [118]), experimental evidence supporting a function in repressing somatic genes expression in the germline and/or promoting maintenance of germ cell fate is lacking.…”

Section: Preventing Reprogramming Of Germ Cells Into Somatic Cell Typmentioning

confidence: 99%

“…Following migration, Dazl-deficient germ cells fail to express markers of male or female differentiation, do not enter meiosis, and eventually undergo apoptosis [133,138]. Very recently, using an in vitro assay consisting of a Dazl-GFP reporter expressed in ESC line to obtain PGC-like cells, Chen et al [117] were able to recover sufficient PGC-like cells for RNA-immunoprecipitation experiments. By this approach, DAZL was shown to bind and directly suppresses specific pluripotency genes, including Sox2, Sall4, and the PRC2 gene Suz12.…”

Section: Dazl Prevents Expression Of Pluripotency Genes and Apoptosismentioning

confidence: 99%

“…SUZ12 is a core component of PRC2 [93,94] and is required for ES cell differentiation [141]. DAZL-mediated silencing of both pluripotency factors and PRC2 may therefore reduce the risk of teratoma formation by inhibiting the pluripotent program while simultaneously preventing somatic differentiation [117]. Interestingly, DAZL also associates with mRNAs of key Caspases to inhibit their translation [117], and Dazl --deficient germ cells show increased apoptosis [138].…”

Section: Dazl Prevents Expression Of Pluripotency Genes and Apoptosismentioning

confidence: 99%

“…DAZL-mediated silencing of both pluripotency factors and PRC2 may therefore reduce the risk of teratoma formation by inhibiting the pluripotent program while simultaneously preventing somatic differentiation [117]. Interestingly, DAZL also associates with mRNAs of key Caspases to inhibit their translation [117], and Dazl --deficient germ cells show increased apoptosis [138]. This raises the possibility that loss of pluripotency regulation simultaneously triggers germ cell death and prevents germ cell tumor formation through an efficient fail-safe mechanism.…”

Section: Dazl Prevents Expression Of Pluripotency Genes and Apoptosismentioning

confidence: 99%

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Repression of somatic cell fate in the germline

Robert

Garvis

Palladino

2015

Cell. Mol. Life Sci.

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Germ cells must transmit genetic information across generations, and produce gametes while also maintaining the potential to form all cell types after fertilization. Preventing the activation of somatic programs is, therefore, crucial to the maintenance of germ cell identity. Studies in Caenorhabditis elegans, Drosophila melanogaster, and mouse have revealed both similarities and differences in how somatic gene expression is repressed in germ cells, thereby preventing their conversion into somatic tissues. This review will focus on recent developments in our understanding of how global or gene-specific transcriptional repression, chromatin regulation, and translational repression operate in the germline to maintain germ cell identity and repress somatic differentiation programs.

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Regulation of ATF1 and ATF2 transcripts by sequences in their 3′ untranslated region in cleavage‐stage cattle embryos

Orozco‐Lucero

Dufort

Sirard

2017

Molecular Reproduction Devel

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The sequence of a 3' untranslated region (3'UTR) of mRNA governs the timing of its polyadenylation and translation in mammalian oocytes and early embryos. The objective of this study was to assess the influence of cis-elements in the 3'UTR of the developmentally important ATF1 and ATF2 transcripts on their timely translation during first cleavages in bovine embryos. Eight different reporter mRNAs (coding sequence of green fluorescent protein [GFP] fused to the 3'UTR of short or long isoforms of cattle ATF1 or -2, with or without polyadenylation) or a control GFP mRNA were microinjected separately into presumptive bovine zygotes at 18 hr post-insemination (hpi), followed by epifluorescence assessment for GFP translation between 24 and 80 hpi (expressed as percentage of GFP-positive embryos calculated from the total number of individuals). The presence of either polyadenine or 3'UTR sequence in deadenylated constructs is required for GFP translation (implying the need for polyadenylation), and all exogenous mRNAs that met either criteria were translated as soon as 24 hpi-except for long-deadenylated ATF2-UTR, whose translation began at 36 hpi. Overall, GFP was more visibly translated in competent (cleaving) embryos, particularly in long ATF1/2 constructs. The current data shows a timely GFP translation in bovine embryos depending on sequences in the 3'UTR of ATF1/2, and indicates a difference between short and long isoforms. In addition, cleaving embryos displayed increased translational capacity of the tested constructs. Functional confirmation of the identification cis-sequences in the 3'UTR of ATF1/2 will contribute to the understanding of maternal mRNA translation regulation during early cattle development.

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DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells

Cited by 85 publications

References 44 publications

The timeline development of female canine germ cells

The timeline development of female canine germ cells

Repression of somatic cell fate in the germline

Regulation of ATF1 and ATF2 transcripts by sequences in their 3′ untranslated region in cleavage‐stage cattle embryos

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