scholarly journals Loss of the histone chaperone ASF1B reduces female reproductive capacity in mice

Reproduction ◽  
2016 ◽  
Vol 151 (5) ◽  
pp. 477-489 ◽  
Author(s):  
S Messiaen ◽  
J Guiard ◽  
C Aigueperse ◽  
I Fliniaux ◽  
S Tourpin ◽  
...  
Keyword(s):  
Gonad Development ◽  
Cell Lineage ◽  
Reproductive Capacity ◽  
Chromatin Modifications ◽  
Mouse Development ◽  
Differentiation Potential ◽  
Female Mice ◽  
Evolutionarily Conserved ◽  
Meiotic Entry

Abstract Anti-silencing function 1 (ASF1) is an evolutionarily conserved histone H3–H4 chaperone involved in the assembly/disassembly of nucleosome and histone modification. Two paralogous genes, Asf1a and Asf1b, exist in the mouse genome. Asf1a is ubiquitously expressed and its loss causes embryonic lethality. Conversely, Asf1b expression is more restricted and has been less studied. To determine the in vivo function of Asf1b, we generated a Asf1b-deficient mouse line (Asf1bGT(ROSA-βgeo)437) in which expression of the lacZ reporter gene is driven by the Asf1b promoter. Analysis of β-galactosidase activity at early embryonic stages indicated a correlation between Asf1b expression and cell differentiation potential. In the gonads of both male and female, Asf1b expression was specifically detected in the germ cell lineage with a peak expression correlated with meiosis. The viability of Asf1b-null mice suggests that Asf1b is dispensable for mouse development. However, these mice showed reduced reproductive capacity compared with wild-type controls. We present evidence that the timing of meiotic entry and the subsequent gonad development are affected more severely in Asf1b-null female mice than in male mice. In female mice, in addition to subfertility related to altered gamete formation, variable defects compromising the development and/or survival of their offspring were also observed. Altogether, our data indicate the importance of Asf1b expression at the time of meiotic entry, suggesting that chromatin modifications may play a central role in this process.

scholarly journals The Drosophila tango gene encodes a bHLH-PAS protein that is orthologous to mammalian Arnt and controls CNS midline and tracheal development

Development ◽  
1997 ◽  
Vol 124 (22) ◽  
pp. 4571-4582 ◽  
Author(s):  
M. Sonnenfeld ◽  
M. Ward ◽  
G. Nystrom ◽  
J. Mosher ◽  
S. Stahl ◽  
...  
Keyword(s):  
Cell Culture ◽  
Gene Dosage ◽  
Cell Lineage ◽  
Regulatory System ◽  
In Vivo Studies ◽  
Enhancer Element ◽  
Evolutionarily Conserved ◽  
Cns Midline ◽  
Functionally Diverse

The Drosophila single-minded and trachealess bHLH-PAS genes control transcription and development of the CNS midline cell lineage and tracheal tubules, respectively. We show that Single-minded and Trachealess activate transcription by forming dimers with the Drosophila Tango protein that is an orthologue of the mammalian Arnt protein. Both cell culture and in vivo studies show that a DNA enhancer element acts as a binding site for both Single-minded::Tango and Trachealess::Tango heterodimers and functions in controlling CNS midline and tracheal transcription. Isolation and analysis of tango mutants reveal CNS midline and tracheal defects, and gene dosage studies demonstrate in vivo interactions between single-minded::tango and trachealess::tango. These experiments support the existence of an evolutionarily conserved, functionally diverse bHLH-PAS protein regulatory system.

scholarly journals Sox9-dependent expression of Gstm6 in Sertoli cells during testis development in mice

Reproduction ◽  
2009 ◽  
Vol 137 (3) ◽  
pp. 481-486 ◽  
Author(s):  
Annemiek Beverdam ◽  
Terje Svingen ◽  
Stefan Bagheri-Fam ◽  
Pascal Bernard ◽  
Peter McClive ◽  
...  
Keyword(s):  
Gonad Development ◽  
Cell Lineage ◽  
Somatic Tissue ◽  
Temporal Expression ◽  
Mouse Development ◽  
Adult Mice ◽  
Multifunctional Enzymes ◽  
Male Sex ◽  
Temporal Expression Pattern ◽  
Male Specific

Glutathione S-transferases (GSTs) are an important family of multifunctional enzymes that play a role in the protection of tissues by the detoxification of hazardous and carcinogenic compounds. We found previously that Gstm6 is upregulated in the somatic cells of male mouse fetal gonads relative to female gonads. In this study, we describe the spatial and temporal expression pattern of Gstm6 during mouse development. We show that Gstm6 is predominantly expressed in the reproductive system, at significantly higher levels in XY gonads compared with XX gonads from 11.5 dpc onwards, and remains expressed in the testes in adult mice. Its expression is associated with the Sertoli cell lineage, and is dependent on the expression of the male sex-determining gene Sox9. Our data suggest that Gstm6 plays a male-specific role in gonad development or function, possibly by modulating the exposure of somatic tissue and/or germ cells to endogenous or exogenous toxicants.

scholarly journals Skeletal muscle phenotypes initiated by ectopic MyoD in transgenic mouse heart

Development ◽  
1992 ◽  
Vol 114 (4) ◽  
pp. 853-860 ◽  
Author(s):  
J.H. Miner ◽  
J.B. Miller ◽  
B.J. Wold
Keyword(s):  
Skeletal Muscle ◽  
Cultured Cells ◽  
Regulatory Gene ◽  
Cell Lineage ◽  
Cardiac Differentiation ◽  
Mouse Heart ◽  
Mouse Development ◽  
Cellular Environment ◽  
Close Relatives

Forced expression of the myogenic regulatory gene MyoD in many types of cultured cells initiates their conversion into skeletal muscle. It is not known, however, if MyoD expression serves to activate all or part of the skeletal muscle program in vivo during animal development, nor is it known how limiting the influences of cellular environment may be on the regulatory effects of MyoD. To begin to address these issues, we have produced transgenic mice which express MyoD in developing heart, where neither MyoD nor its three close relatives—myogenin, Myf-5, and MRF4/herculin/Myf-6—are normally expressed. The resulting gross phenotype in offspring from multiple, independent transgenic founders includes abnormal heart morphology and ultimately leads to death. At the molecular level, affected hearts exhibit activation of skeletal muscle-specific regulatory as well as structural genes. We conclude that MyoD is able to initiate the program that leads to skeletal muscle differentiation during mouse development, even in the presence of the ongoing cardiac differentiation program. Thus, targeted misexpression of this tissue-specific regulator during mammalian embryogenesis can activate, either directly or indirectly, a diverse set of genes normally restricted to a different cell lineage and a different cellular environment.

Evaluation of the In Vivo Acute Toxicity and In Vitro Hemolytic and Immunomodulatory Activities of the Moringa oleifera Flower Trypsin Inhibitor (MoFTI)

2020 ◽  
Vol 27 ◽  
Author(s):  
Leydianne Leite de Siqueira Patriota ◽  
Dayane Kelly Dias do Nascimento Santos ◽  
Bárbara Rafaela da Silva Barros ◽  
Lethícia Maria de Souza Aguiar ◽  
Yasmym Araújo Silva ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Trypsin Inhibitor ◽  
Hemolytic Activity ◽  
Moringa Oleifera ◽  
Biological Activities ◽  
Hematological Parameters ◽  
Behavioral Alterations ◽  
Female Mice

Background: Protease inhibitors have been isolated from plants and present several biological activities, including immunomod-ulatory action. Objective: This work aimed to evaluate a Moringa oleifera flower trypsin inhibitor (MoFTI) for acute toxicity in mice, hemolytic activity on mice erythrocytes and immunomodulatory effects on mice splenocytes. Methods: The acute toxicity was evaluated using Swiss female mice that received a single dose of the vehicle control or MoFTI (300 mg/kg, i.p.). Behavioral alterations were observed 15–240 min after administration, and survival, weight gain, and water and food consumption were analyzed daily. Organ weights and hematological parameters were analyzed after 14 days. Hemolytic activity of MoFTI was tested using Swiss female mice erythrocytes. Splenocytes obtained from BALB/c mice were cultured in the absence or presence of MoFTI for the evaluation of cell viability and proliferation. Mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) levels were also determined. Furthermore, the culture supernatants were analyzed for the presence of cytokines and nitric oxide (NO). Results: MoFTI did not cause death or any adverse effects on the mice except for abdominal contortions at 15–30 min after administration. MoFTI did not exhibit a significant hemolytic effect. In addition, MoFTI did not induce apoptosis or necrosis in splenocytes and had no effect on cell proliferation. Increases in cytosolic and mitochondrial ROS release, as well as ΔΨm reduction, were observed in MoFTI-treated cells. MoFTI was observed to induce TNF-α, IFN-γ, IL-6, IL-10, and NO release. Conclusion: These results contribute to the ongoing evaluation of the antitumor potential of MoFTI and its effects on other immunological targets.

scholarly journals Human Keratinocytes Adopt Neuronal Fates After In Utero Transplantation in the Developing Rat Brain

2021 ◽  
Vol 30 ◽  
pp. 096368972097821
Author(s):  
Andrea Tenorio-Mina ◽  
Daniel Cortés ◽  
Joel Esquivel-Estudillo ◽  
Adolfo López-Ornelas ◽  
Alejandro Cabrera-Wrooman ◽  
...  
Keyword(s):  
Green Fluorescent Protein ◽  
Fluorescent Protein ◽  
Ectopic Expression ◽  
Neural Induction ◽  
Human Keratinocytes ◽  
Differentiation Potential ◽  
Neuronal Proteins ◽  
Green Fluorescent

Human skin contains keratinocytes in the epidermis. Such cells share their ectodermal origin with the central nervous system (CNS). Recent studies have demonstrated that terminally differentiated somatic cells can adopt a pluripotent state, or can directly convert its phenotype to neurons, after ectopic expression of transcription factors. In this article we tested the hypothesis that human keratinocytes can adopt neural fates after culturing them in suspension with a neural medium. Initially, keratinocytes expressed Keratins and Vimentin. After neural induction, transcriptional upregulation of NESTIN, SOX2, VIMENTIN, SOX1, and MUSASHI1 was observed, concomitant with significant increases in NESTIN detected by immunostaining. However, in vitro differentiation did not yield the expression of neuronal or astrocytic markers. We tested the differentiation potential of control and neural-induced keratinocytes by grafting them in the developing CNS of rats, through ultrasound-guided injection. For this purpose, keratinocytes were transduced with lentivirus that contained the coding sequence of green fluorescent protein. Cell sorting was employed to select cells with high fluorescence. Unexpectedly, 4 days after grafting these cells in the ventricles, both control and neural-induced cells expressed green fluorescent protein together with the neuronal proteins βIII-Tubulin and Microtubule-Associated Protein 2. These results support the notion that in vivo environment provides appropriate signals to evaluate the neuronal differentiation potential of keratinocytes or other non-neural cell populations.

scholarly journals The SH2-Containing Inositol Polyphosphate 5-Phosphatase, Ship, Is Expressed During Hematopoiesis and Spermatogenesis

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2753-2759 ◽  
Author(s):  
Qiurong Liu ◽  
Fouad Shalaby ◽  
Jamie Jones ◽  
Denis Bouchard ◽  
Daniel J. Dumont
Keyword(s):  
Primitive Streak ◽  
Inositol Polyphosphate ◽  
Mouse Development ◽  
Developmentally Regulated ◽  
Adult Mice ◽  
Expression Studies ◽  
Cell Culture Systems ◽  
Physiologic Function ◽  
T Cell Maturation

Ship is a recently identified SH2-containing inositol polyphosphate 5-phosphatase that has been implicated as an important signaling molecule in cell-culture systems. To understand the physiologic function of Ship in vivo, we performed expression studies of Ship during mouse development. Results of this study demonstrate the expression of ship to be in late primitive-streak stage embryos (7.5 days postcoitus [dpc]), when hematopoiesis is thought to begin, and the expression is restricted to the hematopoietic lineage in mouse embryo. In adult mice, Ship expression continues to be in the majority of cells from hematopoietic origin, including granulocytes, monocytes, and lymphocytes, and is also found in the spermatids of the testis. Furthermore, the level of Ship expression is developmentally regulated during T-cell maturation. These results suggest a possible role for Ship in the differentiation and maintenance of the hematopoietic lineages and in spermatogenesis.

scholarly journals Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation

Blood ◽  
2012 ◽  
Vol 119 (19) ◽  
pp. 4349-4357 ◽  
Author(s):  
Fanny Guimont-Desrochers ◽  
Geneviève Boucher ◽  
Zhongjun Dong ◽  
Martine Dupuis ◽  
André Veillette ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Adoptive Transfer ◽  
Nk Cell ◽  
Cell Lineage ◽  
Current View ◽  
Antitumoral Activity ◽  
Nk Cell Differentiation ◽  
A Cell

Abstract The cell lineage origin of IFN-producing killer dendritic cells (IKDCs), which exhibit prominent antitumoral activity, has been subject to debate. Although IKDCs were first described as a cell type exhibiting both plasmacytoid DC and natural killer (NK) cell properties, the current view reflects that IKDCs merely represent activated NK cells expressing B220, which were thus renamed B220+ NK cells. Herein, we further investigate the lineage relation of B220+ NK cells with regard to other NK-cell subsets. We surprisingly find that, after adoptive transfer, B220− NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220+ NK cells are activated NK cells. Moreover, we unequivocally show that B220+ NK cells are highly proliferative and differentiate into mature NK cells after in vivo adoptive transfer. Additional phenotypic, functional, and transcriptional characterizations further define B220+ NK cells as immediate precursors to mature NK cells. The characterization of these novel attributes to B220+ NK cells will guide the identification of their ortholog in humans, contributing to the design of potent cancer immunotherapies.

scholarly journals Bax, Caspase-2, and Caspase-3 Are Required for Ovarian Follicle Loss Caused by 4-Vinylcyclohexene Diepoxide Exposure of Female Mice in Vivo

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Yasushi Takai ◽  
Jacqueline Canning ◽  
Gloria I. Perez ◽  
James K. Pru ◽  
Jennifer J. Schlezinger ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Ovarian Follicle ◽  
Female Mice ◽  
Vinylcyclohexene Diepoxide ◽  
Caspase 2

scholarly journals Normal Immune System Development in Mice Lacking the Deltex-1 RING Finger Domain

2005 ◽  
Vol 25 (4) ◽  
pp. 1437-1445 ◽  
Author(s):  
Sébastien Storck ◽  
Frédéric Delbos ◽  
Nicolas Stadler ◽  
Catherine Thirion-Delalande ◽  
Florence Bernex ◽  
...  
Keyword(s):  
B Cell ◽  
Notch Signaling ◽  
Ubiquitin Ligase ◽  
Cell Lineage ◽  
Ring Finger ◽  
Mouse Development ◽  
Ring Finger Domain ◽  
Ubiquitin Ligase Activity ◽  
Immune System Development ◽  
Cell Commitment

ABSTRACT The Notch signaling pathway controls several cell fate decisions during lymphocyte development, from T-cell lineage commitment to the peripheral differentiation of B and T lymphocytes. Deltex-1 is a RING finger ubiquitin ligase which is conserved from Drosophila to humans and has been proposed to be a regulator of Notch signaling. Its pattern of lymphoid expression as well as gain-of-function experiments suggest that Deltex-1 regulates both B-cell lineage and splenic marginal-zone B-cell commitment. Deltex-1 was also found to be highly expressed in germinal-center B cells. To investigate the physiological function of Deltex-1, we generated a mouse strain lacking the Deltex-1 RING finger domain, which is essential for its ubiquitin ligase activity. Deltex-1Δ/Δ mice were viable and fertile. A detailed histological analysis did not reveal any defects in major organs. T- and B-cell development was normal, as were humoral responses against T-dependent and T-independent antigens. These data indicate that the Deltex-1 ubiquitin ligase activity is dispensable for mouse development and immune function. Possible compensatory mechanisms, in particular those from a fourth Deltex gene identified during the course of this study, are also discussed.

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