scholarly journals Conditional Mutagenesis of Gata6 in SF1-Positive Cells Causes Gonadal-Like Differentiation in the Adrenal Cortex of Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1754-1767 ◽  
Author(s):  
Marjut Pihlajoki ◽  
Elisabeth Gretzinger ◽  
Rebecca Cochran ◽  
Antti Kyrönlahti ◽  
Anja Schrade ◽  
...  

Abstract Transcription factor GATA6 is expressed in the fetal and adult adrenal cortex and has been implicated in steroidogenesis. To characterize the role of transcription factor GATA6 in adrenocortical development and function, we generated mice in which Gata6 was conditionally deleted using Cre-LoxP recombination with Sf1-cre. The adrenal glands of adult Gata6 conditional knockout (cKO) mice were small and had a thin cortex. Cytomegalic changes were evident in fetal and adult cKO adrenal glands, and chromaffin cells were ectopically located at the periphery of the glands. Corticosterone secretion in response to exogenous ACTH was blunted in cKO mice. Spindle-shaped cells expressing Gata4, a marker of gonadal stroma, accumulated in the adrenal subcapsule of Gata6 cKO mice. RNA analysis demonstrated the concomitant upregulation of other gonadal-like markers, including Amhr2, in the cKO adrenal glands, suggesting that GATA6 inhibits the spontaneous differentiation of adrenocortical stem/progenitor cells into gonadal-like cells. Lhcgr and Cyp17 were overexpressed in the adrenal glands of gonadectomized cKO vs control mice, implying that GATA6 also limits sex steroidogenic cell differentiation in response to the hormonal changes that accompany gonadectomy. Nulliparous female and orchiectomized male Gata6 cKO mice lacked an adrenal X-zone. Microarray hybridization identified Pik3c2g as a novel X-zone marker that is downregulated in the adrenal glands of these mice. Our findings offer genetic proof that GATA6 regulates the differentiation of steroidogenic progenitors into adrenocortical cells.

2019 ◽  
Vol 167 (4) ◽  
pp. 568-573
Author(s):  
N. V. Yaglova ◽  
S. S. Obernikhin ◽  
S. V. Nazimova ◽  
V. V. Yaglov

2014 ◽  
Vol 127 (7) ◽  
pp. 1428-1440 ◽  
Author(s):  
F. Fang ◽  
S. M. Wasserman ◽  
J. Torres-Vazquez ◽  
B. Weinstein ◽  
F. Cao ◽  
...  

2009 ◽  
Vol 331 (2) ◽  
pp. 436-437
Author(s):  
Dobrawa Napierala ◽  
Izabela Maciejewska ◽  
Elda Munivez ◽  
Brian Dawson ◽  
Rena D'Souza ◽  
...  

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8473
Author(s):  
Xinling Hu ◽  
Lisha Zhang ◽  
Iain Wilson ◽  
Fenjuan Shao ◽  
Deyou Qiu

The MYB transcription factor family is one of the largest gene families playing regulatory roles in plant growth and development. The MYB family has been studied in a variety of plant species but has not been reported in Taxus chinensis. Here we identified 72 putative R2R3-MYB genes in T. chinensis using a comprehensive analysis. Sequence features, conversed domains and motifs were characterized. The phylogenetic analysis showed TcMYBs and AtMYBs were clustered into 36 subgroups, of which 24 subgroups included members from T. chinensis and Arabidopsis thaliana, while 12 subgroups were specific to one species. This suggests the conservation and specificity in structure and function of plant R2R3-MYBs. The expression of TcMYBs in various tissues and different ages of xylem were investigated. Additionally, miRNA-mediated posttranscriptional regulation analysis revealed that TcMYBs were the targets of miR858, miR159 and miR828, suggesting the posttranscriptional regulation of MYBs is highly conserved in plants. The results provide a basis for further study the role of TcMYBs in the regulation of secondary metabolites of T. chinensis.


2013 ◽  
Vol 52 (1) ◽  
pp. R17-R33 ◽  
Author(s):  
Adrien Georges ◽  
Aurelie Auguste ◽  
Laurianne Bessière ◽  
Anne Vanet ◽  
Anne-Laure Todeschini ◽  
...  

Forkhead box L2 (FOXL2) is a gene encoding a forkhead transcription factor preferentially expressed in the ovary, the eyelids and the pituitary gland. Its germline mutations are responsible for the blepharophimosis ptosis epicanthus inversus syndrome, which includes eyelid and mild craniofacial defects associated with primary ovarian insufficiency. Recent studies have shown the involvement of FOXL2 in virtually all stages of ovarian development and function, as well as in granulosa cell (GC)-related pathologies. A central role of FOXL2 is the lifetime maintenance of GC identity through the repression of testis-specific genes. Recently, a highly recurrent somatic FOXL2 mutation leading to the p.C134W subtitution has been linked to the development of GC tumours in the adult, which account for up to 5% of ovarian malignancies. In this review, we summarise data on FOXL2 modulators, targets, partners and post-translational modifications. Despite the progresses made thus far, a better understanding of the impact of FOXL2 mutations and of the molecular aspects of its function is required to rationalise its implication in various pathophysiological processes.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Tao Yu ◽  
Yong Jun Li ◽  
Ai Hong Bian ◽  
Hui Bin Zuo ◽  
Ti Wen Zhu ◽  
...  

Activating transcription factor 2 (ATF2) is a member of the leucine zipper family of DNA-binding proteins and is widely distributed in tissues including the liver, lung, spleen, and kidney. Like c-Jun and c-Fos, ATF2 responds to stress-related stimuli and may thereby influence cell proliferation, inflammation, apoptosis, oncogenesis, neurological development and function, and skeletal remodeling. Recent studies clarify the regulatory role of ATF2 in inflammation and describe potential inhibitors of this protein. In this paper, we summarize the properties and functions of ATF2 and explore potential applications of ATF2 inhibitors as tools for research and for the development of immunosuppressive and anti-inflammatory drugs.


2016 ◽  
Vol 213 (11) ◽  
pp. 2349-2364 ◽  
Author(s):  
Zhenhua Yang ◽  
Kushani Shah ◽  
Alireza Khodadadi-Jamayran ◽  
Hao Jiang

As the major histone H3K4 methyltransferases in mammals, the Set1/Mll complexes play important roles in animal development and are associated with many diseases, including hematological malignancies. However, the role of the H3K4 methylation activity of these complexes in fate determination of hematopoietic stem and progenitor cells (HSCs and HPCs) remains elusive. Here, we address this question by generating a conditional knockout mouse for Dpy30, which is a common core subunit of all Set1/Mll complexes and facilitates genome-wide H3K4 methylation in cells. Dpy30 loss in the adult hematopoietic system results in severe pancytopenia but striking accumulation of HSCs and early HPCs that are defective in multilineage reconstitution, suggesting a differentiation block. In mixed bone marrow chimeras, Dpy30-deficient HSCs cannot differentiate or efficiently up-regulate lineage-regulatory genes, and eventually fail to sustain for long term with significant loss of HSC signature gene expression. Our molecular analyses reveal that Dpy30 directly and preferentially controls H3K4 methylation and expression of many hematopoietic development-associated genes including several key transcriptional and chromatin regulators involved in HSC function. Collectively, our results establish a critical and selective role of Dpy30 and the H3K4 methylation activity of the Set1/Mll complexes for maintaining the identity and function of adult HSCs.


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