Dynamic changes in the subnuclear organisation of pre-mRNA splicing proteins and RBM during human germ cell development

1998 ◽  
Vol 111 (9) ◽  
pp. 1255-1265 ◽  
Author(s):  
D.J. Elliott ◽  
K. Oghene ◽  
G. Makarov ◽  
O. Makarova ◽  
T.B. Hargreave ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Biology ◽  
Rna Binding ◽  
Spatial Association ◽  
Cell Types ◽  
Cell Development ◽  
Mrna Splicing ◽  
Human Testis ◽  
Germ Cell Development ◽  
Nuclear Regions

RBM is a germ-cell-specific RNA-binding protein encoded by the Y chromosome in all mammals, implying an important and evolutionarily conserved (but as yet unidentified) function during male germ cell development. In order to address this function, we have developed new antibody reagents to immunolocalise RBM in the different cell types in the human testis. We find that RBM has a different expression profile from its closest homologue hnRNPG. Despite its ubiquitous expression in all transcriptionally active germ cell types, RBM has a complex and dynamic cell biology in human germ cells. The ratio of RBM distributed between punctate nuclear structures and the remainder of the nucleoplasm is dynamically modulated over the course of germ cell development. Moreover, pre-mRNA splicing components are targeted to the same punctate nuclear regions as RBM during the early stages of germ cell development but late in meiosis this spatial association breaks down. After meiosis, pre-mRNA splicing components are differentially targeted to a specific region of the nucleus. While pre-mRNA splicing components undergo profound spatial reorganisations during spermatogenesis, neither heterogeneous ribonucleoproteins nor the transcription factor Sp1 show either developmental spatial reorganisations or any specific co-localisation with RBM. These results suggest dynamic and possibly multiple functions for RBM in germ cell development.

scholarly journals hnRNPH1 recruits PTBP2 and SRSF3 to cooperatively modulate alternative pre-mRNA splicing in germ cells and is essential for spermatogenesis and oogenesis

2021 ◽  
Author(s):  
Shuiqiao Yuan ◽  
Shenglei Feng ◽  
Jinmei Li ◽  
Hui Wen ◽  
Kuan Liu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Germ Cell ◽  
Germ Cells ◽  
Rna Binding ◽  
Cell Development ◽  
Mrna Splicing ◽  
Conditional Knockout ◽  
Cell Junction ◽  
Germ Cell Development ◽  
Splicing Regulators

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.

scholarly journals Survival Motor Neuron Protein Participates in Mouse Germ Cell Development and Spermatogonium Maintenance

2020 ◽  
Vol 21 (3) ◽  
pp. 794 ◽  
Author(s):  
Wei-Fang Chang ◽  
Jie Xu ◽  
Tzu-Ying Lin ◽  
Jing Hsu ◽  
Hsiu-Mei Hsieh-Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Motor Neuron ◽  
Cell Biology ◽  
Critical Role ◽  
Embryonic Stem ◽  
Cell Development ◽  
Survival Motor Neuron ◽  
Specific Marker ◽  
Germ Cell Development

The defective human survival motor neuron 1 (SMN1) gene leads to spinal muscular atrophy (SMA), the most common genetic cause of infant mortality. We previously reported that loss of SMN results in rapid differentiation of Drosophila germline stem cells and mouse embryonic stem cells (ESCs), indicating that SMN also plays important roles in germ cell development and stem cell biology. Here, we show that in healthy mice, SMN is highly expressed in the gonadal tissues, prepubertal spermatogonia, and adult spermatocytes, whereas low SMN expression is found in differentiated spermatid and sperm. In SMA-like mice, the growth of testis tissues is retarded, accompanied with gamete development abnormalities and loss of the spermatogonia-specific marker. Consistently, knockdown of Smn1 in spermatogonial stem cells (SSCs) leads to a compromised regeneration capacity in vitro and in vivo in transplantation experiments. In SMA-like mice, apoptosis and accumulation of the R-loop structure were significantly elevated, indicating that SMN plays a critical role in the survival of male germ cells. The present work demonstrates that SMN, in addition to its critical roles in neuronal development, participates in mouse germ cell and spermatogonium maintenance.

nos-1 and nos-2, two genes related to Drosophila nanos, regulate primordial germ cell development and survival in Caenorhabditis elegans

Development ◽  
1999 ◽  
Vol 126 (21) ◽  
pp. 4861-4871 ◽  
Author(s):  
K. Subramaniam ◽  
G. Seydoux
Keyword(s):  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Primordial Germ Cell ◽  
Gene Families ◽  
Cell Development ◽  
Embryonic Patterning ◽  
Germ Cell Development ◽  
C Elegans

In Drosophila, the posterior determinant nanos is required for embryonic patterning and for primordial germ cell (PGC) development. We have identified three genes in Caenorhabditis elegans that contain a putative zinc-binding domain similar to the one found in nanos, and show that two of these genes function during PGC development. Like Drosophila nanos, C. elegans nos-1 and nos-2 are not generally required for PGC fate specification, but instead regulate specific aspects of PGC development. nos-2 is expressed in PGCs around the time of gastrulation from a maternal RNA associated with P granules, and is required for the efficient incorporation of PGCs into the somatic gonad. nos-1 is expressed in PGCs after gastrulation, and is required redundantly with nos-2 to prevent PGCs from dividing in starved animals and to maintain germ cell viability during larval development. In the absence of nos-1 and nos-2, germ cells cease proliferation at the end of the second larval stage, and die in a manner that is partially dependent on the apoptosis gene ced-4. Our results also indicate that putative RNA-binding proteins related to Drosophila Pumilio are required for the same PGC processes as nos-1 and nos-2. These studies demonstrate that evolutionarily distant organisms utilize conserved factors to regulate early germ cell development and survival, and that these factors include members of the nanos and pumilio gene families.

scholarly journals 50 years of spermatogenesis: Sertoli cells and their interactions with germ cells

2018 ◽  
Vol 99 (1) ◽  
pp. 87-100 ◽  
Author(s):  
Michael D Griswold
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Cultured Cells ◽  
Cell Types ◽  
Cell Development ◽  
Specific Cell ◽  
Germ Cell Development ◽  
Cell Niche ◽  
Transgenic Technologies

Abstract The complex morphology of the Sertoli cells and their interactions with germ cells has been a focus of investigators since they were first described by Enrico Sertoli. In the past 50 years, information on Sertoli cells has transcended morphology alone to become increasingly more focused on molecular questions. The goal of investigators has been to understand the role of the Sertoli cells in spermatogenesis and to apply that information to problems relating to male fertility. Sertoli cells are unique in that they are a nondividing cell population that is active for the reproductive lifetime of the animal and cyclically change morphology and gene expression. The numerous and distinctive junctional complexes and membrane specializations made by Sertoli cells provide a scaffold and environment for germ cell development. The increased focus of investigators on the molecular components and putative functions of testicular cells has resulted primarily from procedures that isolate specific cell types from the testicular milieu. Products of Sertoli cells that influence germ cell development and vice versa have been characterized from cultured cells and from the application of transgenic technologies. Germ cell transplantation has shown that the Sertoli cells respond to cues from germ cells with regard to developmental timing and has furthered a focus on spermatogenic stem cells and the stem cell niche. Very basic and universal features of spermatogenesis such as the cycle of the seminiferous epithelium and the spermatogenic wave are initiated by Sertoli cells and maintained by Sertoli-germ cell cooperation.

006. HUMAN GERM CELL FORMATION AND DIFFERENTIATION FROM PLURIPOTENT STEM CELLS

2010 ◽  
Vol 22 (9) ◽  
pp. 5
Author(s):  
R. A. ReijoPiera
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Germ Cells ◽  
Pluripotent Stem Cells ◽  
Rna Binding ◽  
Cell Formation ◽  
Cell Development ◽  
Model Organisms ◽  
Germ Cell Development ◽  
Germ Cell Formation

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.

RNA binding protein Musashi‐1 directly targets Msi2 and Erh during early testis germ cell development and interacts with IPO5 upon translocation to the nucleus

2015 ◽  
Vol 29 (7) ◽  
pp. 2759-2768 ◽  
Author(s):  
Jessie M. Sutherland ◽  
Alexander P. Sobinoff ◽  
Barbara A. Fraser ◽  
Kate A. Redgrove ◽  
Tara‐Lynne Davidson ◽  
...  
Keyword(s):  
Germ Cell ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cell Development ◽  
Germ Cell Development

scholarly journals Disorganization of the germ cell pool leads to primary ovarian insufficiency

Reproduction ◽  
2017 ◽  
Vol 153 (6) ◽  
pp. R205-R213 ◽  
Author(s):  
Ikko Kawashima ◽  
Kazuhiro Kawamura
Keyword(s):  
Germ Cell ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Primordial Follicle ◽  
Cell Development ◽  
Primary Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Germ Cell Development ◽  
Female Germ Cell

The mammalian ovary is an organ that controls female germ cell development, storing them and releasing mature oocytes for transporting to the oviduct. During the fetal stage, female germ cells change from a proliferative state to meiosis before forming follicles with the potential for the growth of surrounding somatic cells. Understanding of molecular and physiological bases of germ cell development in the fetal ovary contributed not only to the elucidation of genetic disorders in primary ovarian insufficiency (POI), but also to the advancement of novel treatments for patients with POI. Accumulating evidence indicates that mutations inNOBOX,DAZLandFIGLAgenes are associated with POI. In addition, cell biology studies revealed the important roles of these genes as essential translational factors for germ cell development. Recent insights into the role of the PI3K (phosphatidylinositol 3-kinase)-Akt signaling pathway in primordial follicle activation allowed the development of a new infertility treatment, IVA (in vitroactivation), leading to successful pregnancy/delivery in POI patients. Furthermore, elucidation of genetic dynamics underlying female germ cell development could allow regeneration of oocytes from ES (embryonic stem)/iPS (induced pluripotent stem) cells in mammals. The purpose of this review is to summarize basic findings related to female germ cell development and potential clinical implications, especially focusing on POI etiologies. We also summarize evolving new POI therapies based on IVA as well as oocyte regeneration.

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