scholarly journals On the role of germ cells in mammalian gonad development: quiet passengers or back-seat drivers?

Reproduction ◽  
2015 ◽  
Vol 149 (4) ◽  
pp. R181-R191 ◽  
Author(s):  
Clarissa Rios-Rojas ◽  
Josephine Bowles ◽  
Peter Koopman
Keyword(s):  
Germ Cells ◽  
Cell Biology ◽  
Gonad Development ◽  
Careful Analysis ◽  
Gonadal Development ◽  
Cell Phenotype ◽  
Open Questions ◽  
Endocrine Organs ◽  
And Function ◽  
Molecular Signals

In addition to their role as endocrine organs, the gonads nurture and protect germ cells, and regulate the formation of gametes competent to convey the genome to the following generation. After sex determination, gonadal somatic cells use several known signalling pathways to direct germ cell development. However, the extent to which germ cells communicate back to the soma, the molecular signals they use to do so and the significance of any such signalling remain as open questions. Herein, we review findings arising from the study of gonadal development and function in the absence of germ cells in a range of organisms. Most published studies support the view that germ cells are unimportant for foetal gonadal development in mammals, but later become critical for stabilisation of gonadal function and somatic cell phenotype. However, the lack of consistency in the data, and clear differences between mammals and other vertebrates and invertebrates, suggests that the story may not be so simple and would benefit from more careful analysis using contemporary molecular, cell biology and imaging tools.

scholarly journals N-Cadherin Is Critical for the Survival of Germ Cells, the Formation of Steroidogenic Cells, and the Architecture of Developing Mouse Gonads

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1610 ◽  
Author(s):  
Rafal P. Piprek ◽  
Michal Kolasa ◽  
Dagmara Podkowa ◽  
Malgorzata Kloc ◽  
Jacek Z. Kubiak
Keyword(s):  
Germ Cells ◽  
Hormonal Regulation ◽  
Critical Role ◽  
Somatic Cells ◽  
Gonad Development ◽  
Knock Out ◽  
Gonad Differentiation ◽  
Steroidogenic Cells ◽  
The Individual ◽  
And Function

Normal gonad development assures the fertility of the individual. The properly functioning gonads must contain a sufficient number of the viable germ cells, possess a correct architecture and tissue structure, and assure the proper hormonal regulation. This is achieved by the interplay between the germ cells and different types of somatic cells. N-cadherin coded by the Cdh2 gene plays a critical role in this interplay. To gain an insight into the role of N-cadherin in the development of mouse gonads, we used the Cre-loxP system to knock out N-cadherin separately in two cell lines: the SF1+ somatic cells and the OCT4+ germ cells. We observed that N-cadherin plays a key role in the survival of both female and male germ cells. However, the N-cadherin is not necessary for the differentiation of the Sertoli cells or the initiation of the formation of testis cords or ovigerous cords. In the later stages of gonad development, N-cadherin is important for the maintenance of testis cord structure and is required for the formation of steroidogenic cells. In the ovaries, N-cadherin is necessary for the formation of the ovarian follicles. These results indicate that N-cadherin plays a major role in gonad differentiation, structuralization, and function.

scholarly journals Interspecific hybridization of sturgeon species affects differently their gonadal development

2017 ◽  
Vol 63 (No. 1) ◽  
pp. 1-10 ◽  
Author(s):  
Z. Linhartová ◽  
M. Havelka ◽  
M. Pšenička ◽  
M. Flajšhans
Keyword(s):  
Interspecific Hybridization ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Interspecific Hybrids ◽  
Gonad Development ◽  
Gonadal Development ◽  
Genetic Origin ◽  
Ploidy Levels ◽  
Sturgeon Species ◽  
Fertile Hybrids

Gonad development in fish is generally assumed to be negatively influenced by interspecific hybridization, resulting in sterility or sub-sterility. However, this is not the case in sturgeons (Acipenseridae), in which fertile hybrids are common. In the present study, we investigated gonad development in several sturgeon interspecific hybrids and purebred species. Six interspecific hybrid groups and three purebred groups were analyzed including 20 hybrid specimens with even ploidy, 40 specimens having odd ploidy levels, and 30 purebred specimens. Hybrids of species with the same ploidy (even ploidy – 2n, 4n) exhibited normally developed gonads similar to those seen in purebred specimens. In contrast, hybrids of species differing in ploidy (odd ploidy – 3n) did not display fully developed gonads. Ovaries were composed of oocytes or nests of differentiating oocytes that ceased development in early stages of meiosis (pachytene to zygotene) with a higher content of adipose and apoptotic tissue. Testes contained single spermatogonia along with Sertoli cells and spaces lacking germ cells. The obtained results showed that gonad development was influenced by genetic origin and ploidy of the sturgeon hybrids and were consistent with full fertility of hybrids with even ploidy. Sterility of females, but possibly limited fertility of males, is suggested for hybrids with odd ploidy.

scholarly journals Different expression and activity of the α1 and α4 isoforms of the Na,K-ATPase during rat male germ cell ontogeny

Reproduction ◽  
2005 ◽  
Vol 130 (5) ◽  
pp. 627-641 ◽  
Author(s):  
K Wagoner ◽  
G Sanchez ◽  
A-N Nguyen ◽  
G C Enders ◽  
G Blanco
Keyword(s):  
Plasma Membrane ◽  
Germ Cell ◽  
Germ Cells ◽  
Cell Biology ◽  
Mrna Level ◽  
Male Gamete ◽  
Male Germ Cell ◽  
Male Germ Cells ◽  
And Function ◽  
Expression And Activity

Two catalytic isoforms of the Na,K-ATPase, α1 and α4, are present in testis. While α1 is ubiquitously expressed in tissues, α4 predominates in male germ cells. Each isoform has distinct enzymatic properties and appears to play specific roles. To gain insight into the relevance of the Na,K-ATPase α isoforms in male germ cell biology, we have studied the expression and activity of α1 and α4 during spermatogenesis and epididymal maturation. This was explored in rat testes at different ages, in isolated spermatogenic cells and in spermatozoa from the caput and caudal regions of the epididymis. Our results show that α1 and α4 undergo differential regulation during development. Whereas α1 exhibits only modest changes, α4 increases with gamete differentiation. The most drastic changes for α4 take place in spermatocytes at the mRNA level, and with the transition of round spermatids into spermatozoa for expression and activity of the protein. No further changes are detected during transit of spermatozoa through the epididymis. In addition, the cellular distribution of α4 is modified with development, being diffusely expressed at the plasma membrane and intracellular compartments of immature cells, finally to localize to the midregion of the spermatozoon flagellum. In contrast, the α1 isoform is evenly present along the plasma membrane of the developing and mature gametes. In conclusion, the Na,K-ATPase α1 and α4 isoforms are functional in diploid, meiotic and haploid male germ cells, α4 being significantly upregulated during spermatogenesis. These results support the importance of α4 in male gamete differentiation and function.

scholarly journals Expression of Wsb2 in the developing and adult mouse testis

Reproduction ◽  
2007 ◽  
Vol 133 (4) ◽  
pp. 753-761 ◽  
Author(s):  
M A Sarraj ◽  
P J McClive ◽  
A Szczepny ◽  
H Daggag ◽  
K L Loveland ◽  
...  
Keyword(s):  
Real Time ◽  
Germ Cells ◽  
Adult Mouse ◽  
Gonad Development ◽  
Gonadal Development ◽  
Mouse Testis ◽  
Hedgehog Signalling ◽  
Real Time Analysis ◽  
Female Specific ◽  
Male Specific

We present a detailed study of the expression pattern of WD repeat and SOCS box-containing 2 (Wsb2) in mouse embryonic and adult gonads. Wsb2 was previously identified in a differential screen aimed at identifying the genes involved in male- and female-specific gonadal development. Wsb2 expression was analysed during mouse gonadogenesis by real-time PCR, whole-mount and section in situ hybridisation and immunofluorescence. Wsb2 mRNA expression was initially detected in gonads of both sexes from 11.5 days post coitum (dpc) until 12.0 dpc. By 12.5 dpc and thereafter, Wsb2 expression rapidly decreased in the female, while persisting in the male gonads. In foetal, newborn and juvenile testes, Wsb2 mRNA and protein were readily detected in the seminiferous cords within both Sertoli and germ cells. Wsb2 mRNA was present in spermatogonia, spermatocytes and in Sertoli cells of the adult mouse testis. The differential expression of Wsb2 in male versus female embryonic gonads suggests some male-specific role in gonad development, and its expression in the first wave of spermatogenesis indicates a role in germ cells. Real-time analysis of adult mouse testis tubules cultured in the presence of the Hedgehog signalling inhibitor, cyclopamine, showed a downregulation of Wsb2 mRNA after treatment which suggests that Wsb2 may be a target of Hedgehog signalling.

Cell Morphology and Migration of Nucleus Pulposus Cells Depends on Substrate Stiffness and Ligand

2012 ◽  
Author(s):  
Priscilla Y. Hwang ◽  
Christopher L. Gilchrist ◽  
Aubrey T. Francisco ◽  
Jun Chen ◽  
Lori A. Setton
Keyword(s):  
Nucleus Pulposus ◽  
Cell Biology ◽  
Imaging Techniques ◽  
Matrix Proteins ◽  
Cell Phenotype ◽  
Nucleus Pulposus Cells ◽  
Cell Clustering ◽  
And Migration ◽  
And Function

Changes in nucleus pulposus (NP) cell phenotype and morphology are implicated in the progression of intervertebral disc (IVD) disorders. Understanding how changes in the NP cell microenvironment influence cell behavior and function is important for revealing how pathology-related changes in IVD extracellular matrix may affect NP cell biology. In this study, live-cell imaging techniques were utilized to study changes in cell migration and morphology when cultured upon substrates of different matrix proteins and stiffnesses. Results indicate that soft substrates containing matrix proteins promote cell clustering and cell-cell interactions which mimic in vivo conditions of healthy NP cells.

scholarly journals Strategies to Overcome Failures in T-Cell Immunotherapies by Targeting PI3K-δ and –γ

2021 ◽  
Vol 12 ◽  
Author(s):  
Sanjay Chandrasekaran ◽  
Christopher Ronald Funk ◽  
Troy Kleber ◽  
Chrystal M. Paulos ◽  
Mala Shanmugam ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Biology ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Cell Phenotype ◽  
Future Directions ◽  
Cell Therapies ◽  
T Cell Biology ◽  
And Function ◽  
Cell Inhibition

PI3K-δ and PI3K-γ are critical regulators of T-cell differentiation, senescence, and metabolism. PI3K-δ and PI3K-γ signaling can contribute to T-cell inhibition via intrinsic mechanisms and regulation of suppressor cell populations, including regulatory T-cells and myeloid derived suppressor cells in the tumor. We examine an exciting new role for using selective inhibitors of the PI3K δ- and γ-isoforms as modulators of T-cell phenotype and function in immunotherapy. Herein we review the current literature on the implications of PI3K-δ and -γ inhibition in T-cell biology, discuss existing challenges in adoptive T-cell therapies and checkpoint blockade inhibitors, and highlight ongoing efforts and future directions to incorporate PI3K-δ and PI3K-γ as synergistic T-cell modulators in immunotherapy.

scholarly journals 021.Identification and study of genes important for fetal germ cell biology in mice

2004 ◽  
Vol 16 (9) ◽  
pp. 21
Author(s):  
P. Koopman ◽  
C. Browne ◽  
A. Jackson ◽  
K. Ewen ◽  
R. J. Aitken ◽  
...  
Keyword(s):  
Germ Cells ◽  
Cell Biology ◽  
Expression Profiles ◽  
Transcriptional Profiling ◽  
Gonad Development ◽  
Screening Methods ◽  
Pluripotent Cells ◽  
Proteomic Approach

We are using a multi-pronged approach to discovering genes and proteins that regulate the allocation, proliferation, migration, differentiation and apoptosis of primordial germ cells (PGCs) in the developing mouse embryo. First, we are using suppression PCR and microarray screening methods to identify genes whose expression is restricted to, or enriched in, gonads of a specific sex or developmental stage. In this way several genes were identified whose expression is restricted to germ cells. Second, we are using a proteomic approach to identify important proteins and the genes that encode them. Protein expression profiles are being compared between different sexes and stages of mouse fetal gonad development. Data so far indicate that this method is a useful adjunct to transcriptional profiling, capable of identifying not only proteins that are differentially expressed, but also those that are differentially modified, for example by phosphorylation. Third, in silico screening of mouse EST databases identified 23 new candidate genes whose expression appears to be limited to pluripotent cells and the germline. Many of these genes are novel uncharacterised transcripts. Preliminary in situ expression analyses show that eight of these genes are indeed limited to the germline and to pluripotent cells. These genes may have important functions in germline specification and function. We are currently developing approaches, including inducible RNAi-based methods, for examining the function of these genes, initially in vitro but also ultimately in vivo.

scholarly journals Charge-altering releasable transporters enable phenotypic manipulation of natural killer cells for cancer immunotherapy

2020 ◽  
Vol 4 (17) ◽  
pp. 4244-4255 ◽  
Author(s):  
Aaron J. Wilk ◽  
Nancy Lynn-Benner Weidenbacher ◽  
Rosemary Vergara ◽  
Ole A. W. Haabeth ◽  
Ronald Levy ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Cell Biology ◽  
Messenger Rna ◽  
Viral Vectors ◽  
Cell Activation ◽  
Nk Cell ◽  
Clinical Applications ◽  
Cell Phenotype ◽  
And Function

Abstract Chimeric antigen receptor (CAR) natural killer (NK) cells are an emerging cell therapy with promising results in oncology trials. However, primary human NK cells are difficult to transfect, hampering both mechanistic studies and clinical applications of NK cells. Currently, NK cell CAR modification relies on viral vectors or cell activation. The former raises cost and tolerability issues, while the latter alters NK cell biology. Here, we report that readily synthesized and inexpensive nonviral charge-altering releasable transporters (CARTs) efficiently transfect primary human NK cells with messenger RNA without relying on NK cell activation. Compared with electroporation, CARTs transfect NK cells more efficiently, better preserve cell viability, and cause minimal reconfiguration of NK cell phenotype and function. We use CARTs to generate cytotoxic primary anti-CD19 CAR NK cells, demonstrating this technology can drive clinical applications of NK cells. To our knowledge, CARTs represent the first efficacious transfection technique for resting primary human NK cells that preserves NK cell phenotype and can enable new biological discoveries and therapeutic applications of this understudied lymphocyte subset.

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