scholarly journals Somatic regulation of female germ cell regeneration and development in planarians

2021 ◽  
Author(s):  
Umair W. Khan ◽  
Phillip A Newmark

Female germ cells develop into oocytes, with the capacity for totipotency. In most animals, these remarkable cells are specified during development and cannot be regenerated. By contrast, planarians, known for their regenerative prowess, can regenerate germ cells. To uncover mechanisms required for female germ cell development and regeneration, we generated gonad-specific transcriptomes and identified genes whose expression defines progressive stages of female germ cell development. Strikingly, early female germ cells share molecular signatures with the pluripotent stem cells driving planarian regeneration. We uncovered spatial heterogeneity within somatic ovarian cells and found that a regionally enriched FoxL homolog is required for oocyte differentiation, but not specification, suggestive of functionally distinct somatic compartments. Unexpectedly, a neurotransmitter-biosynthetic enzyme, AADC, is also expressed in somatic gonadal cells, and plays opposing roles in female and male germ cell development. Thus, somatic gonadal cells deploy conserved factors to regulate germ cell development and regeneration in planarians.

Author(s):  
Zheng-Hui Zhao ◽  
Jun-Yu Ma ◽  
Tie-Gang Meng ◽  
Zhen-Bo Wang ◽  
Wei Yue ◽  
...  

ABSTRACTFemale germ cell development consists of complex events including sex determination, meiosis initiation, retardation and resumption. During early oogenesis, the asynchrony of the transition from mitosis to meiosis results in heterogeneity in the female germ cell populations at a certain embryonic stage, which limits the studies of meiosis initiation and progression at a higher resolution level. Here, we investigated the transcriptional profiles of 19363 single germ cells collected from E12.5, E14.5 and E16.5 mouse fetal ovaries. Clustering analysis identified seven groups and defined dozens of corresponding transcription factors, providing a global view of cellular differentiation from primordial germ cells towards meiocytes. Further, we explored the dynamics of gene expression within the developmental trajectory with special focus on the mechanisms underlying meiotic initiation. We found that Dpy30 may be involved in the regulation of meiosis initiation at the epigenetic level. Our data provide key insights into the transcriptome features of peri-meiotic female germ cells, which offers new information not only on meiosis initiation and progression but also on screening pathogenic mutations in meiosis-associated diseases.


2010 ◽  
Vol 22 (9) ◽  
pp. 5
Author(s):  
R. A. ReijoPiera

Human embryo development begins with the fusion of egg and sperm, followed by reprogramming of the DNA, a series of cell divisions and activation of the embryo’s genome. As development continues, the germ cells (egg and sperm) must be set aside from other cell types. A major cause of infertility in men and women is quantitative and qualitative defects in human germ cell (oocyte and sperm) development. Yet, it has been difficult to study human germ cell development, especially features that are unique relative to model organisms. We have developed a system to differentiate human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) to germ cells and to quantitate and isolate primordial germ cells (PGCs) derived from both XX- and XY-bearing hESCs and iPSCs. This allowed silencing and overexpression of genes that encode germ cell-specific cytoplasmic RNA-binding proteins (not transcription factors) and resulted in the modulation of human male and female germ cell formation and developmental progression. We observed that human DAZL (Deleted in AZoospermia-Like) functions in female and male PGC formation and maintenance, whereas closely-related family members, BOULE and DAZ, promote entry into meiosis and development of haploid gametes with sperm-specific methylation patterns at imprinted loci in the male. We also conducted critical proof-of-concept studies in mice that showed that phenotypes observed in germ cell development in vitro from wildtype, heterozygous, and Dazl–/– mutation-carrying mouse ESCs (mESCs) mirrored the phenotypes that were observed in vivo. Furthermore, transplantation of XX mESC-derived oocytes resulted in recruitment of somatic cells to form follicles. These studies comprised the first direct experimental analysis of the genetics of human germ cell development and set the stage for extensive exploration of complex genetic variants linked to infertility. Results are significant to the generation of gametes for developmental genetic studies and potential clinical applications.


Development ◽  
1996 ◽  
Vol 122 (3) ◽  
pp. 937-950 ◽  
Author(s):  
K.A. Clark ◽  
D.M. McKearin

The differentiation of Drosophila germ cells is a useful model for studying mechanisms of cell specification. We report the identification of a gene, stonewall, that is required for germ cell development. Mutations in stonewall block proper oocyte differentiation and frequently cause the presumptive oocyte to develop as a nurse cell. Eventually, germ cells degenerate apoptotically. Stonewall is a germ cell nuclear protein; Stonewall has a DNA binding domain that shows similarities to the Myb and Adf-1 transcription factors and has other features that suggest that it is a transcription activating factor. We suggest that Stonewall transcriptional regulation is essential in cystocytes for maturation into specialized nurse cells and oocyte.


2008 ◽  
Vol 78 (Suppl_1) ◽  
pp. 64-64
Author(s):  
Jillian Guttormsen ◽  
Gerrit J. Bouma ◽  
Frances Bhushan ◽  
Trevor Williams ◽  
Quinton A. Winger

2021 ◽  
Author(s):  
Shuiqiao Yuan ◽  
Shenglei Feng ◽  
Jinmei Li ◽  
Hui Wen ◽  
Kuan Liu ◽  
...  

Abstract Coordinated regulation of alternative pre-mRNA splicing is essential for germ cell development. However, the molecular mechanism underlying that control alternative mRNA expression during germ cell development remains poorly understood. Herein, we showed that hnRNPH1, an RNA-binding protein, is highly expressed in the reproductive system and localized in the chromosomes of meiotic cells but excluded from the XY body in pachytene spermatocytes and recruits the splicing regulators PTBP2 and SRSF3 and cooperatively regulates the alternative splicing of the critical genes that are required for spermatogenesis. Conditional knockout Hnrnph1 in spermatogenic cells caused many abnormal splicing events that affect genes related to meiosis and communication between germ cells and Sertoli cells, characterized by asynapsis of chromosomes and impairment of germ-Sertoli communications, ultimately leading to male sterility. We further showed that hnRNPH1 could directly bind to SPO11 and recruit the splicing regulators PTBP2 and SRSF3 to regulate the alternative splicing of the target genes cooperatively. Strikingly, Hnrnph1 germline-specific mutant female mice were also infertile, and Hnrnph1-deficient oocytes exhibited a similar defective synapsis and cell-cell junction as shown in Hnrnph1-deficient male germ cells. Collectively, our data reveal an essential role for hnRNPH1 in regulating pre-mRNA splicing during spermatogenesis and oogenesis and support a molecular model whereby hnRNPH1 governs a network of alternative splicing events in germ cells via recruiting PTBP2 and SRSF3.


Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 229-240 ◽  
Author(s):  
D.L. Chapman ◽  
D.J. Wolgemuth

A cDNA encoding the murine cyclin B2 (cycB2) was isolated from an adult mouse testis cDNA library as part of studies designed to identify cyclins involved in murine germ cell development. This cycB2 cDNA was then used to examine the pattern of cycB2 expression during male and female germ cell development and in early embryogenesis, and to compare this expression with the previously characterized expression of cycB1. A single 1.7 kb cycB2 transcript was detected by northern blot hybridization analysis of total RNA isolated from midgestation embryos and various adult tissues. Northern blot and in situ hybridization analyses revealed that cycB2 expression in the testis was most abundant in the germ cells, specifically in pachytene spermatocytes. This is in contrast to the highest levels of expression of cycB1 being present in early spermatids. In situ analysis of the ovary revealed cycB2 transcripts in both germ cells and somatic cells, specifically in the oocytes and granulosa cells of growing and mature follicles. The pattern of cycB1 and cycB2 expression in ovulated and fertilized eggs was also examined. While the steady state level of cycB1 and cycB2 signal remained constant in oocytes and ovulated eggs, signal of both appeared to decrease following fertilization. In addition, both cycB1 and cycB2 transcripts were detected in the cells of the inner cell mass and the trophectoderm of the blastocyst. These results demonstrate that there are lineage- and developmental-specific differences in the pattern of the B cyclins in mammalian germ cells, in contrast to the co-expression of B cyclins in the early conceptus.


Author(s):  
Jin Zhang ◽  
Juan Dong ◽  
Weibing Qin ◽  
Congcong Cao ◽  
Yujiao Wen ◽  
...  

AbstractOvol2, a mouse homolog of Drosophila ovo, was identified as a zinc finger transcription factor predominantly expressed in testis. However, the function of Ovol2 in postnatal male germ cell development remains enigmatic. Here, we firstly examined the mRNA and protein levels of Ovol2 in developing mouse testes by RT-qPCR and western blot and found that both mRNA and protein of Ovol2 are continually expressed in postnatal developing testes from postnatal day 0 (P0) testes to adult testes (P56) and exhibits its higher level at adult testis. Further testicular immuno-staining revealed that OVOL2 is highly expressed in the spermatogonia, spermatocytes and round spermatids. Interestingly, our conditional ovol2 knockout mouse model show that loss of ovol2 in embryonic germ cells does not affect fecundity in mice. Our data also show that Ovol1 may have compensated for the loss of Ovol2 functions in germ cells. Overall, our data indicate that ovol2 is dispensable for germ cell development and spermatogenesis.


2020 ◽  
Vol 103 (4) ◽  
pp. 717-735
Author(s):  
Yohei Hayashi ◽  
Masaru Mori ◽  
Kaori Igarashi ◽  
Keiko Tanaka ◽  
Asuka Takehara ◽  
...  

Abstract Regulatory mechanisms of germline differentiation have generally been explained via the function of signaling pathways, transcription factors, and epigenetic regulation; however, little is known regarding proteomic and metabolomic regulation and their contribution to germ cell development. Here, we conducted integrated proteomic and metabolomic analyses of fetal germ cells in mice on embryonic day (E)13.5 and E18.5 and demonstrate sex- and developmental stage-dependent changes in these processes. In male germ cells, RNA processing, translation, oxidative phosphorylation, and nucleotide synthesis are dominant in E13.5 and then decline until E18.5, which corresponds to the prolonged cell division and more enhanced hyper-transcription/translation in male primordial germ cells and their subsequent repression. Tricarboxylic acid cycle and one-carbon pathway are consistently upregulated in fetal male germ cells, suggesting their involvement in epigenetic changes preceding in males. Increased protein stability and oxidative phosphorylation during female germ cell differentiation suggests an upregulation of aerobic energy metabolism, which likely contributes to the proteostasis required for oocyte maturation in subsequent stages. The features elucidated in this study shed light on the unrevealed mechanisms of germ cell development.


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