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Schematic anatomy models of mouse and human embryo. (A) Mouse embryo can be visualized as a thick-walled cup of tissue at E6.25-6.5. Polarizing signals determine an anterior-posterior axis and a proximal-distal axis, and then the epiblast region where pPGCs are located. At E7-7.25, gastrulation starts and PGCs arise in the base of allantois by BMP signaling from the ExE. Then the PGCs migrate and at approximately E10.0 reach the gonadal ridges. (B) In humans, at 9 days postcoitum (dpc), the embryo consists of a bilaminar disc, the epiblast and hypoblast. Epiblast form the amnios, but no equivalent structure to the mouse ExE is apparently formed in the human embryo. BMP signals coming from the hypoblast, cytotrophoblast, and probably from amnioblast or both, and pPGCs have been suggested to emerge from the proximal epiblast near the position of the primitive streak (17 dpc). Similar to mice, the PGCs reach the gonad around 33 dpc, after migration. AVE, anterior visceral endoderm; DEc, distal ectoderm; ExE, extraembryonic ectoderm; PEc, proximal ectoderm; PPEc, posterior proximal ectoderm; pPGCs, primordial germ cell precursors; VE, visceral endoderm.
Source publication
Germ line development is crucial in organisms with sexual reproduction to complete their life cycle. In mammals, knowledge about germ line development is based mainly on the mouse model, in which genetic and epigenetic events are well described. However, little is known about how germ line development is orchestrated in humans, especially in the ea...
Contexts in source publication
Context 1
... by contrast, the embryo consists of a bilaminar disc, the epiblast, and the primitive endoderm or hypoblast. The epiblast cells will form the amnioblast and the amniotic cavity [59], whereas the polar trophectoderm over the epiblast differentiates to- ward the syncytiotrophoblast and the cytotrophoblast, which remain in contact with the epiblast (Fig. 2). In other words, no equivalent structure to the mouse ExE, from which PGC specification is triggered, is apparently formed in the human embryo ...
Context 2
... these precursors migrate to the extraembryonic mesoderm and reach the region of the yolk sac where the allantois is formed at around 16 dpc [59]. Then, during the fourth week of gestation, PGCs are passively incorporated into the embryo with the yolk sac wall by folding the em- bryonic disc, and they start to migrate toward the gonadal ridges (Fig. ...
Citations
... The identification of marker genes in germ cells is an initiating step for studying their development. Germ cell development is crucial in organisms with sexual reproduction to complete their life cycle [7]. Vasa is one of the most studied universal markers and is used to identify the germ cells [8]. ...
Vasa (Ddx4, DEAD box polypeptide 4), an extremely specific marker of germ cells in vivo, is an ATP-dependent RNA helicase that plays an essential role in germ cell development and gametogenesis. However, the expression and function information about this gene in groupers remains lacking. Here, vasa homolog termed Plvasa was isolated and identified Plvasa as a putative germ cell marker in the leopard coral grouper, (Plectropomus leopardus). Results indicated that Plvasa contained 17 exons in the genomic sequence and 9 conserved motifs of the DEAD-box protein by sequence analysis. The sequence comparison, phylogenetic analyses and synteny analyses showed that Plvasa was homologous with other teleosts. Additionally, the expression of Plvasa was significantly higher in gonads than in other tissues in adult individuals (p < 0.05). Further, the distribution of Plvasa revealed that it was only expressed in the germ cells, such as spermatids, germline stem cells and oocytes at different stages, and could not be detected in the somatic cells of gonads. The current study verified that the Plvasa gene is a valuable molecular marker of germ cells in leopard coral grouper, which potentially plays an important role in investigating the genesis and development of teleost germ cells.
... We have identified several genes in sarcoma samples that are network neighbors of ctag1b/a including ranbp2, tle1, six1 and prame and using independent sarcoma samples, we immunohistochemically confirmed expression of the encoded proteins for tle1 and ranbp2. Finally, the confirmation of expression of ranbp2 and tle1 as well as the presence of six1 in its network neighborhood suggests that ctag1b/a may be part of transcriptional proteins that functionally interact with proteins involved in sumoylation (via ranbp2) and the cell cycle (via six1, pasd1 and zic3) in sarcoma biology (Liu et al., 2018;Martínez-Arroyo et al., 2015;Ono et al., 2001;Türeci et al., 1998;Xu et al., 2015). ...
Here we describe the identification of genes and their encoded proteins that are expressed in advanced grade tumors by reconstruction of a sarcoma cancer testis gene 1b/a (catg1b/a) network. CTAG1B/A is an ortholog of the yeast/Drosophila transcription factor Pcc1p, and a member of the KEOPS transcription complex. It has been implicated in telomere maintenance and transcriptional regulation through association with chromatin remodeling factors and is only expressed during adult testis germ cell differentiation. Ctag1b/a is re-activated in synovial sarcomas and myxoid liposarcomas but not in differentiated liposarcomas. We mapped CTAG1B/A protein to sarcoma transcription pathways with gene set expression analysis (GSEA) and using independent samples, we immunohistochemically identified expression of at least two network neighbors, RANBP2, and TLE1, thus validating our approach. This work demonstrates that mapping unknown genes to functional pathways by network re-construction is a powerful tool that can be used to identify candidate oncoproteins.
... Scientists have tested different strategies in attempts to form artificial gametes from several cell types, with PSCs being used most frequently. Recent reviews have addressed this issue, and we will not duplicate these efforts (Hendriks et al., 2015;Moreno et al., 2015;Martínez-Arroyo et al., 2015;Vassena et al., 2015;Zeng et al., 2015). Instead, we will focus on the recent work by Sasaki and colleagues; that work, to our knowledge, has made the most significant progress so far in the search for an in vitro differentiation strategy from pluripotent cells to PGCs (Sasaki et al., 2015). ...
Primordial germ cells (PGCs) have long been considered the link between one generation and the next. PGC specification begins in the early embryo as a result of a highly orchestrated combination of transcriptional and epigenetic mechanisms. Understanding the molecular events that lead to proper PGC development will facilitate the development of new treatments for human infertility as well as species conservation. This article describes the latest, most relevant findings about the mechanisms of PGC formation, emphasizing human PGC. It also discusses our own laboratory's progress in using transdifferentiation protocols to derive human PGCs (hPGCs). Our preliminary results arose from our pursuit of a sequential hPGC induction strategy that starts with the repression of lineage-specific factors in the somatic cell, followed by the reactivation of germ cell-related genes using specific master regulators, which can indeed reactivate germ cell-specific genes in somatic cells. While it is still premature to assume that fully functional human gametes can be obtained in a dish, our results, together with those recently published by others, provide strong evidence that generating their precursors, PGCs, is within reach.
