Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during mouse gonadal development and is a potent activator of the Mullerian inhibiting substance promoter

Development ◽  
1998 ◽  
Vol 125 (14) ◽  
pp. 2665-2675 ◽  
Author(s):  
R.S. Viger ◽  
C. Mertineit ◽  
J.M. Trasler ◽  
M. Nemer

Mammalian gonadal development and sexual differentiation are complex processes that require the coordinated expression of a specific set of genes in a strict spatiotemporal manner. Although some of these genes have been identified, the molecular pathways, including transcription factors, that are critical for the early events of lineage commitment and sexual dimorphism, remain poorly understood. GATA-4, a member of the GATA family of transcription factors, is present in the gonads and may be a regulator of gonadal gene expression. We have analyzed the ontogeny of gonadal GATA-4 expression by immunohistochemistry. GATA-4 protein was detected as early as embryonic day 11.5 in the primitive gonads of both XX and XY mouse embryos. In both sexes, GATA-4 specifically marked the developing somatic cell lineages (Sertoli in testis and granulosa in ovary) but not primordial germ cells. Interestingly, abundant GATA-4 expression was maintained in Sertoli cells throughout embryonic development but was markedly down-regulated shortly after the histological differentiation of the ovary on embryonic day 13.5. This pattern of expression suggested that GATA-4 might be involved in early gonadal development and possibly sexual dimorphism. Consistent with this hypothesis, we found that the Mullerian inhibiting substance promoter which harbors a conserved GATA element is a downstream target for GATA-4. Thus, transcription factor GATA-4 may be a new factor in the cascade of regulators that control gonadal development and sex differentiation in mammals.

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3931-3936 ◽  
Author(s):  
Imane Al-Asaad ◽  
Dominique Chardard ◽  
Nathalie di Clemente ◽  
Jean-Yves Picard ◽  
Hélène Dumond ◽  
...  

Müllerian inhibiting substance (MIS, also known as anti-Müllerian hormone), is a key factor of male sex differentiation in vertebrates. In amniotes, it is responsible for Müllerian duct regression in male embryos. In fish, despite the absence of Müllerian ducts, MIS is produced and controls germ cell proliferation during gonad differentiation. Here we show for the first time the presence of MIS in an amphibian species, Pleurodeles waltl. This is very astonishing because in caudate amphibians, Müllerian ducts do not regress in males. Phylogenetic analysis of MIS P. waltl ortholog revealed that the deduced protein segregates with MIS from other vertebrates and is clearly separated from other TGF-β family members. In larvae, MIS mRNA was expressed at higher levels in the developing testes than in the ovaries. In the testis, MIS mRNA expression was located within the lobules that contain Sertoli cells. Besides, expression of MIS was modified in the case of sex reversal: it increased after masculinizing heat treatment and decreased after estradiol feminizing exposure. In addition to the data obtained recently in the fish medaka, our results suggest that the role of MIS on Müllerian ducts occurred secondarily during the course of evolution.


2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Paulina A. Latos ◽  
Angela Goncalves ◽  
David Oxley ◽  
Hisham Mohammed ◽  
Ernest Turro ◽  
...  

Abstract Esrrb (oestrogen-related receptor beta) is a transcription factor implicated in embryonic stem (ES) cell self-renewal, yet its knockout causes intrauterine lethality due to defects in trophoblast development. Here we show that in trophoblast stem (TS) cells, Esrrb is a downstream target of fibroblast growth factor (Fgf) signalling and is critical to drive TS cell self-renewal. In contrast to its occupancy of pluripotency-associated loci in ES cells, Esrrb sustains the stemness of TS cells by direct binding and regulation of TS cell-specific transcription factors including Elf5 and Eomes. To elucidate the mechanisms whereby Esrrb controls the expression of its targets, we characterized its TS cell-specific interactome using mass spectrometry. Unlike in ES cells, Esrrb interacts in TS cells with the histone demethylase Lsd1 and with the RNA Polymerase II-associated Integrator complex. Our findings provide new insights into both the general and context-dependent wiring of transcription factor networks in stem cells by master transcription factors.


Author(s):  
M. Balaganesan ◽  
K. Karalmarx ◽  
R. Jeya Shakila

Background: The existence of two distinct forms within a species that differ in one or more characteristics is known as dimorphism. The gonads are the primary organs in teleost to show sexual dimorphism. Lepidocephalus thermalis belongs to the Cobitidae family. No expression study on the developmental stages was done on this species. Since there is no specific primers reported for L. thermalis, the study has been carried out with the help of the specific primers of catfish. Methods: qRT- PCR is an acknowledged method for gene expression analysis due to its precision and reproducibility. In the current study, the expression of 14 different transcription factors involved in sex differentiation of Indian spiny loach during different developmental stages was analyzed using qRT- PCR and has been compared among the different stages of gonadal development for that transcription factor. Results: Gene expression patterns have been obtained from the total RNA isolated from MSG (Meso nephric gonadal complex), medium stage ovary, medium stage testis, large stage ovary and large stage testis. From the study, it has been analyzed that only sf1 has higher expression in testis and all the other transcription factors has shown higher expression in ovary.


2021 ◽  
pp. 1-18
Author(s):  
Boudjema Imarazene ◽  
Séverine Beille ◽  
Elodie Jouanno ◽  
Adéle Branthonne ◽  
Violette Thermes ◽  
...  

The genetic regulatory network governing vertebrate gonadal differentiation appears less conserved than previously thought. Here, we investigated the gonadal development of Astyanax mexicanus Pachón cavefish by looking at primordial germ cells (PGCs) migration and proliferation, gonad histology, and gene expression patterns. We showed that PGCs are first detected at the 80% epiboly stage and then reach the gonadal primordium at 1 day post-fertilization (dpf). However, in contrast to the generally described absence of PGCs proliferation during their migration phase, PGCs number in cavefish doubles between early neurula and 8–9 somites stages. Combining both gonadal histology and vasa (germ cell marker) expression patterns, we observed that ovarian and testicular differentiation occurs around 65 dpf in females and 90 dpf in males, respectively, with an important inter-individual variability. The expression patterns of dmrt1, gsdf, and amh revealed a conserved predominant male expression during cavefish gonadal development, but none of the ovarian differentiation genes, i. e., foxl2a, cyp19a1a, and wnt4b displayed an early sexually dimorphic expression, and surprisingly all these genes exhibited predominant expression in adult testes. Altogether, our results lay the foundation for further research on sex determination and differentiation in A. mexicanus and contribute to the emerging picture that the vertebrate sex differentiation downstream regulatory network is less conserved than previously thought, at least in teleost fishes.


2002 ◽  
Vol 175 (2) ◽  
pp. 365-374 ◽  
Author(s):  
SA McCoard ◽  
TH Wise ◽  
JJ Ford

Sexual differentiation and early embryonic/fetal gonad development is a tightly regulated process controlled by numerous endocrine and molecular signals. These signals ensure appropriate structural organization and subsequent development of gonads and accessory organs. Substantial differences exist in adult reproductive characteristics in Meishan (MS) and White Composite (WC) pig breeds. This study compared the timing of embryonic sexual differentiation in MS and WC pigs. Embryos/fetuses were evaluated on 26, 28, 30, 35, 40 and 50 days postcoitum (dpc). Gonadal differentiation was based on morphological criteria and on localization of GATA4, Mullerian-inhibiting substance (MIS) and 17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450(c17)). The timing of testicular cord formation and functional differentiation of Sertoli and Leydig cells were similar between breeds. Levels of GATA4, MIS and P450(c17) proteins increased with advancing gestation, with greater levels of MIS and P450(c17) in testes of MS compared with WC embryos. Organization of ovarian medullary cords and formation of egg nests was evident at similar ages in both breeds; however, a greater number of MS compared with WC embryos exhibited signs of ovarian differentiation at 30 dpc. In summary, despite breed differences in MIS and P450(c17) levels in the testis, which may be related to Sertoli and Leydig cell function, the timing of testicular differentiation did not differ between breeds and is unlikely to impact reproductive performance in adult boars. In contrast, female MS embryos exhibited advanced ovarian differentiation compared with WC embryos which may be related to the earlier reproductive maturity observed in this breed.


Reproduction ◽  
2016 ◽  
Vol 152 (5) ◽  
pp. 575-589 ◽  
Author(s):  
Shigeo Otake ◽  
Min Kyun Park

Gonadal sex differentiation proceeds by the interplay of various genes including the transcription factors and secretory factors in a complex network. The sex-differentiating genes are expressed not only during early sex differentiation but also throughout the gonadal development and even in the adult gonads. In addition, the evidence that they actually function in the adult gonads have been accumulated from the studies using the conditional knockout mice. However, many previous studies were focused on one single gene though those genes function in a network. In this study, the expressions of various sex-differentiating genes were analyzed simultaneously in the adult testis of the Japanese quail (Coturnix japonica), whose testicular functions are dramatically changed by altering the photoperiod, to elucidate the roles of them in the adult gonad. Anti-Müllerian hormone (AMH) was significantly upregulated in the regressed testis induced by the short-day condition. The expressions of the transcription factors that promoteAMHexpression in mammals (SF1,SOX9,WT1andGATA4) were also increased in the regressed testis. Moreover, AMH receptor (AMHR2) showed similar expression pattern to its ligand. We also analyzed the expressions of other transforming growth factor beta (TGFB) superfamily members and their receptors. The expressions of the ligands and receptors of TGFB family, and follistatin and betaglycan in addition to inhibin subunits were increased in the regressed testis. These results suggest that AMH is involved in the adult testicular functions of the Japanese quail together with other TGFB superfamily members.


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