scholarly journals Critical role of Emx2 in the pluripotency – differentiation transition in male gonocytes via regulation of FGF9/NODAL pathway

Reproduction ◽  
2016 ◽  
Vol 151 (6) ◽  
pp. 673-681 ◽  
Author(s):  
Ma Tian-Zhong ◽  
Chen Bi ◽  
Zhang Ying ◽  
Jing Xia ◽  
Peng Cai-Ling ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Mouse Model ◽  
Germ Cell ◽  
Germ Cells ◽  
Critical Role ◽  
Genital Ridge ◽  
Germ Cell Differentiation ◽  
Pluripotency Markers

Abstract Emx2 deletion impairs the growth and maintenance of the genital ridge. However, its role in subsequent germ cell differentiation during embryonic stages is unknown. Using a tamoxifen-inducible Cre-loxP mouse model (Emx2flox/flox, Cre-ERTM, hereafter called as Emx2 knockdown), we showed that germ cell differentiation was impaired in Emx2-knockdown testes. Representative characteristics of male germ cell differentiation, including a reduced ability to form embryonic germ (EG) cell colonies in vitro, down-regulation of pluripotency markers and G1/G0 arrest, did not occur in Emx2-knockdown testes. Furthermore, FGF9 and NODAL signalling occurred at abnormally high levels in Emx2-knockdown testes. Both blocking FGF9 signalling with SU5402 and inhibiting NODAL signalling with SB431542 allowed germ cells from Emx2-knockdown testes to differentiate in vitro. Therefore, EMX2 in somatic cells is required to trigger germ cell differentiation in XY foetuses, posterior to its previously reported role in the growth and maintenance of the genital ridge.

scholarly journals Abnormal Meiosis Initiation in Germ Cell Caused by Aberrant Differentiation of Gonad Somatic Cell

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Min Chen ◽  
Min Chen ◽  
Suren Chen ◽  
Jingjing Zhou ◽  
Fangfang Dong ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Germ Cell ◽  
Somatic Cell ◽  
Germ Cells ◽  
Somatic Cells ◽  
Ectopic Expression ◽  
Genital Ridge ◽  
Male And Female ◽  
Germ Cell Differentiation ◽  
Exact Function

The interaction between germ cell and somatic cell plays important roles in germ cell development. However, the exact function of gonad somatic cell in germ cell differentiation is unclear. In the present study, the function of gonad somatic cell in germ cell meiosis was examined by using mouse models with aberrant somatic cell differentiation. In Wt1R394W/R394W mice, the genital ridge is absent due to the apoptosis of coelomic epithelial cells. Interestingly, in both male and female Wt1R394W/R394W germ cells, STRA8 was detected at E12.5 and the scattered SYCP3 foci were observed at E13.5 which was consistent with control females. In Wt1-/flox; Cre-ERTM mice, Wt1 was inactivated by the injection of tamoxifen at E9.5 and the differentiation of Sertoli and granulosa cells was completely blocked. We found that most germ cells were located outside of genital ridge after Wt1 inactivation. STRA8, SYCP3, and γH2AX proteins were detected in germ cells of both male and female Wt1-/flox; Cre-ERTM gonads, whereas no thread-like SYCP3 signal was observed. Our study demonstrates that aberrant development of gonad somatic cells leads to ectopic expression of meiosis-associated genes in germ cells, but meiosis was arrested before prophase I. These results suggest that the proper differentiation of gonad somatic cells is essential for germ cell meiosis.

Role of Mael in early oogenesis and during germ-cell differentiation from embryonic stem cells in mice in vitro

Zygote ◽  
2013 ◽  
Vol 22 (4) ◽  
pp. 513-520 ◽  
Author(s):  
I. Bahena ◽  
E. Xu ◽  
M. Betancourt ◽  
E. Casas ◽  
Y. Ducolomb ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Differentiation ◽  
Embryonic Stem Cells ◽  
Germ Cell ◽  
Embryonic Stem ◽  
Oocyte Growth ◽  
Germ Cell Differentiation ◽  
Rnai Technology

SummaryIn a previous study, we have identified a set of conserved spermatogenic genes whose expression is restricted to testis and ovary and that are developmentally regulated. One of these genes, the transcription factor Mael, has been reported to play an essential role in mouse spermatogenesis. Nevertheless, the role of Mael in mouse oogenesis has not been defined. In order to analyse the role of Mael in mouse oogenesis, the expression of this gene was blocked during early oogenesis in mouse in vitro using RNAi technology. In addition, the role of Mael during differentiation of embryonic stem cells (ESC) into germ cells in vitro was analysed. Results show that downregulation of Mael by a specific short interfering RNA disrupted fetal oocyte growth and differentiation in fetal ovary explants in culture and the expression of several germ-cell markers in ESC during their differentiation. These results suggest that there is an important role for Mael in early oogenesis and during germ-cell differentiation from embryonic stem cells in mouse in vitro.

scholarly journals Evolving Role of RING1 and YY1 Binding Protein in the Regulation of Germ-Cell-Specific Transcription

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 941 ◽  
Author(s):  
Izabella Bajusz ◽  
Surya Henry ◽  
Enikő Sutus ◽  
Gergő Kovács ◽  
Melinda K. Pirity
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
Germ Cell ◽  
Binding Protein ◽  
Es Cells ◽  
Critical Role ◽  
Embryonic Stem ◽  
Germ Cell Differentiation ◽  
Germline Cells

Separation of germline cells from somatic lineages is one of the earliest decisions of embryogenesis. Genes expressed in germline cells include apoptotic and meiotic factors, which are not transcribed in the soma normally, but a number of testis-specific genes are active in numerous cancer types. During germ cell development, germ-cell-specific genes can be regulated by specific transcription factors, retinoic acid signaling and multimeric protein complexes. Non-canonical polycomb repressive complexes, like ncPRC1.6, play a critical role in the regulation of the activity of germ-cell-specific genes. RING1 and YY1 binding protein (RYBP) is one of the core members of the ncPRC1.6. Surprisingly, the role of Rybp in germ cell differentiation has not been defined yet. This review is focusing on the possible role of Rybp in this process. By analyzing whole-genome transcriptome alterations of the Rybp-/- embryonic stem (ES) cells and correlating this data with experimentally identified binding sites of ncPRC1.6 subunits and retinoic acid receptors in ES cells, we propose a model how germ-cell-specific transcription can be governed by an RYBP centered regulatory network, underlining the possible role of RYBP in germ cell differentiation and tumorigenesis.

scholarly journals Hedgehog signalling promotes germ cell survival in the rat testis

Reproduction ◽  
2011 ◽  
Vol 142 (5) ◽  
pp. 711-721 ◽  
Author(s):  
Juho-Antti Mäkelä ◽  
Vuokko Saario ◽  
Sonia Bourguiba-Hachemi ◽  
Mirja Nurmio ◽  
Kirsi Jahnukainen ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Germ Cell ◽  
Germ Cells ◽  
Tyrosine Kinases ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Paracrine Signalling ◽  
Rat Testis ◽  
Germ Cell Differentiation

Hedgehog (Hh) signalling has a crucial role in testis development. Sertoli cell-derived desert hedgehog (DHH) guides the formation of testis cords and differentiation of foetal-type Leydig cells. Dhh mutant mice are infertile due to a block in germ cell differentiation, hypogonadism and hypoandrogenism. Hh signalling pathway components are also expressed in postnatal testis. In the rat testis the transcription factor of the Hh pathway, glioma-associated oncogene homologue (GLI1), is expressed by a wide variety of germ cells. This suggests that Hh signalling is involved in spermatogenesis at many different levels. Our data show that canonical Hh signalling is turned off in early condensing spermatids that strongly express the negative regulator of the pathway, suppressor of fused (SUFU). Most of the Hh pathway specific mRNAs display the highest values in stages II–VI of the rat seminiferous epithelial cycle. The key endocrine regulator of germ cell differentiation, FSH, down-regulates Dhh mRNA levels in vitro. Hh signalling inhibition in vitro leads to massive apoptosis of germ cells. In prepubertal rat testis imatinib mesylate-induced inhibition of tyrosine kinases impinges on Dhh transcript levels and Hh signalling. Our data indicate that Hh signalling is part of the paracrine signalling network in the rat testis. It promotes the survival of germ cells and is suppressed by FSH.

scholarly journals Mitochondrial fission regulates germ cell differentiation by suppressing ROS-mediated activation of Epidermal Growth Factor Signaling in the Drosophila larval testis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rafael Sênos Demarco ◽  
D. Leanne Jones
Keyword(s):  
Cell Differentiation ◽  
Germ Cell ◽  
Germ Cells ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Germline Stem Cell ◽  
Mitochondrial Morphology ◽  
Mitochondrial Network ◽  
Germ Cell Differentiation

AbstractMitochondria are essential organelles that have recently emerged as hubs for several metabolic and signaling pathways in the cell. Mitochondrial morphology is regulated by constant fusion and fission events to maintain a functional mitochondrial network and to remodel the mitochondrial network in response to external stimuli. Although the role of mitochondria in later stages of spermatogenesis has been investigated in depth, the role of mitochondrial dynamics in regulating early germ cell behavior is relatively less-well understood. We previously demonstrated that mitochondrial fusion is required for germline stem cell (GSC) maintenance in the Drosophila testis. Here, we show that mitochondrial fission is also important for regulating the maintenance of early germ cells in larval testes. Inhibition of Drp1 in early germ cells resulted in the loss of GSCs and spermatogonia due to the accumulation of reactive oxygen species (ROS) and activation of the EGFR pathway in adjacent somatic cyst cells. EGFR activation contributed to premature germ cell differentiation. Our data provide insights into how mitochondrial dynamics can impact germ cell maintenance and differentiation via distinct mechanisms throughout development.

scholarly journals Cell-type-specific regulation of genes involved in testicular lipid metabolism: fatty acid-binding proteins, diacylglycerol acyltransferases, and perilipin 2

Reproduction ◽  
2013 ◽  
Vol 146 (5) ◽  
pp. 471-480 ◽  
Author(s):  
Gerardo M Oresti ◽  
Jesús García-López ◽  
Marta I Aveldaño ◽  
Jesús del Mazo
Keyword(s):  
Fatty Acid ◽  
Cell Differentiation ◽  
Germ Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Fatty Acid Binding Proteins ◽  
Cell Type ◽  
Fatty Acid Binding ◽  
Germ Cell Differentiation ◽  
Perilipin 2

Male germ cell differentiation entails the synthesis and remodeling of membrane polar lipids and the formation of triacylglycerols (TAGs). This requires fatty acid-binding proteins (FABPs) for intracellular fatty acid traffic, a diacylglycerol acyltransferase (DGAT) to catalyze the final step of TAG biosynthesis, and a TAG storage mode. We examined the expression of genes encoding five members of the FABP family and two DGAT proteins, as well as the lipid droplet protein perilipin 2 (PLIN2), during mouse testis development and in specific cells from seminiferous epithelium.Fabp5expression was distinctive of Sertoli cells and consequently was higher in prepubertal than in adult testis. The expression ofFabp3increased in testis during postnatal development, associated with the functional differentiation of interstitial cells, but was low in germ cells.Fabp9, together withFabp12, was prominently expressed in the latter. Their transcripts increased from spermatocytes to spermatids and, interestingly, were highest in spermatid-derived residual bodies (RB). Both Sertoli and germ cells, which produce neutral lipids and store them in lipid droplets, expressedPlin2. Yet, whileDgat1was detected in Sertoli cells,Dgat2accumulated in germ cells with a similar pattern of expression asFabp9. These results correlated with polyunsaturated fatty acid-rich TAG levels also increasing with mouse germ cell differentiation highest in RB, connecting DGAT2 with the biosynthesis of such TAGs. The age- and germ cell type-associated increases inFabp9,Dgat2, andPlin2levels are thus functionally related in the last stages of germ cell differentiation.

scholarly journals Interactome analyses reveal profound proteasome structural and functional rearrangements throughout mammalian spermatogenesis

2021 ◽  
Author(s):  
Dusan Zivkovic ◽  
Angelique Sanchez Dafun ◽  
Thomas Menneteau ◽  
Adrien Schahl ◽  
Sandrine Lise ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Germ Cell ◽  
Germ Cells ◽  
Protein Assembly ◽  
Homologous Chromosomes ◽  
High Proteolytic Activity ◽  
Complex Processes ◽  
Germ Cell Differentiation ◽  
Mechanism Function

During spermatogenesis, spermatogonia undergo a series of mitotic and meiotic divisions on their path to spermatozoa. To achieve this, a succession of complex processes requiring high proteolytic activity are in part orchestrated by the proteasome. The spermatoproteasome (s20S) is a proteasome subtype specific to the developing gametes, in which the gamete-specific α4s subunit replaces the α4 isoform found in the constitutive proteasome (c20S). Although the s20S is conserved across species and was shown to be crucial for germ cell development, its mechanism, function and structure remain incompletely characterized. Here, we used advanced mass spectrometry (MS) methods to map the composition of proteasome complexes and their interactomes throughout spermatogenesis. We observed that the s20S becomes highly activated as germ cells enter meiosis, mainly through association with proteasome activators PA200 and 19S. Additionally, the proteasome population shifts from predominantly c20S (98%) to predominantly s20S (>82-92%) during differentiation, presumably due to the shift from α4 to α4s expression. We confirmed that s20S, but not c20S, interacts with components of the synaptonemal complex, the multi-protein assembly that connects homologous chromosomes during meiosis. In vitro, s20S preferentially bind to 19S, and displayed higher trypsin- and chymotrypsin-like activities, both with and without PA200 activation. Moreover, using MS methods to monitor protein dynamics, we identified significant differences in domain flexibility between α4 and α4s. We propose that these differences induced by α4s incorporation result in significant changes in the way the s20S interacts with its partners, and dictate its role in germ cell differentiation.

Role of Sex Chromosomes in the Control of Male Germ-Cell Differentiation

1991 ◽  
Vol 637 (1 The Male Germ) ◽  
pp. 64-73 ◽  
Author(s):  
MARY HANDEL ◽  
PATRICIA A. HUNT ◽  
MARY C. KOT ◽  
CYNTHIA PARK ◽  
MARK SHANNON
Keyword(s):  
Cell Differentiation ◽  
Germ Cell ◽  
Sex Chromosomes ◽  
Male Germ Cell ◽  
Germ Cell Differentiation
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