The molecular genetics of Sry and its role in mammalian sex determination

1995 ◽  
Vol 350 (1333) ◽  
pp. 205-214 ◽  
Keyword(s):  
Sex Determination ◽  
Target Genes ◽  
Gene Action ◽  
Human Gene ◽  
Cell Lineage ◽  
Supporting Cell ◽  
Gonadal Development ◽  
Genital Ridge ◽  
Testis Differentiation ◽  
Testicular Differentiation

The process of sex determination, by which is meant the decision as to whether an embryo develops as a male or a female, is considered as a paradigm of how gene action can influence developmental fate. In mammals the decision is dependent on the action of the testis determining gene present on the Y chromosome, now known to be the gene Sry . Sry is expressed for only a brief period in the mouse embryo and must act to initiate rather than maintain the pathway of gene activity required for testis differentiation. It probably acts within cells of the supporting cell lineage to direct their differentiation into Sertoli cells, rather than the granulosa cells characteristic of the ovary. Other lineages in the gonad then follow the male pathway. The nature of the Sry transcript in the genital ridge of mice has been determined and compared with that from the human gene which is dramatically different. The expression of Sry has been carefully examined during the critical stages of genital ridge development and compared to the expression of a number of other genes involved in gonadal development and male development such as that for anti-Mullerian hormone. This has defined the period in which Sry must act to between 11 and 11.5 days post coitum . The expression of Sry has also been examined in cases of sex reversal in the mouse. There is a dependence on level of expression and extent of testicular differentiation that suggests thresholds for both the amount of SRY per cell and the number of cells expressing the gene. The SRY protein interacts with DNA through an HMG box type of DNA binding domain, however at present no definite target genes have been found. Progress on strategies to find such genes is discussed.

Origin and function of embryonic Sertoli cells

2011 ◽  
Vol 2 (6) ◽  
pp. 537-547 ◽  
Author(s):  
Francisco Barrionuevo ◽  
Miguel Burgos ◽  
Rafael Jiménez
Keyword(s):  
Sertoli Cells ◽  
Molecular Mechanisms ◽  
Cell Lineage ◽  
Supporting Cell ◽  
Seminiferous Tubules ◽  
Adult Testis ◽  
Myoid Cell ◽  
Testis Development ◽  
Regulatory Processes ◽  
Testis Differentiation

AbstractIn the adult testis, Sertoli cells (SCs) are the epithelial supporting cells of the seminiferous tubules that provide germ cells (GCs) with the required nutrients and structural and regulatory support to complete spermatogenesis. SCs also form the blood-testis barrier, phagocytose apoptotic spermatocytes and cell debris derived from spermiogenesis, and produce and secrete numerous paracrine and endocrine signals involved in different regulatory processes. In addition to their essential functions in the adult testis, SCs play a pivotal role during testis development. They are the first cells to differentiate in the embryonic XY gonadal primordium and are involved in the regulation of testis-specific differentiation processes, such as prevention of GC entry into meiosis, Leydig and peritubular myoid cell differentiation, and regression of the Müllerian duct, the anlagen of the uterus, oviducts, and the upper part of the vagina. Expression of the Y-linked gene SRY in pre-SCs initiates a genetic cascade that leads to SC differentiation and subsequently to testis development. Since the identification of the SRY gene, many Sertoli-specific transcription factors and signals underlying the molecular mechanisms of early testis differentiation have been identified. Here, we review the state of the art of the molecular interactions that commit the supporting cell lineage of the gonadal primordium to differentiate as SCs and the subsequent Sertoli-specific signaling pathways involved in early testis differentiation.

scholarly journals PAX2+ Mesenchymal Origin of Gonadal Supporting Cells Is Conserved in Birds

2021 ◽  
Vol 9 ◽  
Author(s):  
Martin A. Estermann ◽  
Mylene M. Mariette ◽  
Julie L. M. Moreau ◽  
Alexander N. Combes ◽  
Craig A. Smith
Keyword(s):  
Cell Differentiation ◽  
Sex Differentiation ◽  
Cell Lineage ◽  
Mesenchymal Cell ◽  
Supporting Cell ◽  
Gonadal Development ◽  
Supporting Cells ◽  
Mesenchymal Origin ◽  
Germ Cell Differentiation ◽  
Pax2 Expression

During embryonic gonadal development, the supporting cell lineage is the first cell type to differentiate, giving rise to Sertoli cells in the testis and pre-granulosa cells in the ovary. These cells are thought to direct other gonadal cell lineages down the testis or ovarian pathways, including the germline. Recent research has shown that, in contrast to mouse, chicken gonadal supporting cells derive from a PAX2/OSR1/DMRT1/WNT4 positive mesenchymal cell population. These cells colonize the undifferentiated genital ridge during early gonadogenesis, around the time that germ cells migrate into the gonad. During the process of somatic gonadal sex differentiation, PAX2 expression is down-regulated in embryonic chicken gonads just prior to up-regulation of testis- and ovary-specific markers and prior to germ cell differentiation. Most research on avian gonadal development has focused on the chicken model, and related species from the Galloanserae clade. There is a lack of knowledge on gonadal sex differentiation in other avian lineages. Comparative analysis in birds is required to fully understand the mechanisms of avian sex determination and gonadal differentiation. Here we report the first comparative molecular characterization of gonadal supporting cell differentiation in birds from each of the three main clades, Galloanserae (chicken and quail), Neoaves (zebra finch) and Palaeognathe (emu). Our analysis reveals conservation of PAX2+ expression and a mesenchymal origin of supporting cells in each clade. Moreover, down-regulation of PAX2 expression precisely defines the onset of gonadal sex differentiation in each species. Altogether, these results indicate that gonadal morphogenesis is conserved among the major bird clades.

scholarly journals Functional analysis of Mmd2 and related PAQR genes during sex determination in mice

2021 ◽  
Author(s):  
Liang Zhao ◽  
Ella Thomson ◽  
Ee Ting Ng ◽  
Enya Longmuss ◽  
Terje Svingen ◽  
...  
Keyword(s):  
Sex Determination ◽  
Cell Lineage ◽  
Gonadal Development ◽  
Extensive Study ◽  
Mouse Strains ◽  
Loss Of Function ◽  
Expression Screening ◽  
Testis Development ◽  
Sex Development ◽  
Differences Of Sex Development

Sex determination in eutherian mammals is controlled by the Y-linked gene Sry, which drives the formation of testes in male embryos. Despite extensive study, the genetic steps linking Sry action and male sex determination remain largely unknown. Here, we focused on Mmd2, a gene that encodes a member of the progestin and adipoQ receptor (PAQR) family. We show that Mmd2 is expressed during the sex-determining period in XY but not XX gonads, specifically in the Sertoli cell lineage which orchestrates early testis development. Analysis of knockout mice deficient in Sox9 and Sf1 revealed that Mmd2 operates downstream of these known sex-determining genes. However, when we used CRISPR to ablate Mmd2 in the mouse, fetal testis development appeared to progress normally. To determine if other genes might have compensated for the loss of Mmd2, we identified the closely related PAQR family members Paqr8 and Mmd as also being expressed during testis development. We used CRISPR to generate mouse strains deficient in Paqr8 and Mmd, but both knockout lines appeared phenotypically normal and fertile. Finally, we generated Mmd2;Mmd and Mmd2;Paqr8 double-null embryos and again observed normal testis development. These results may reflect functional redundancy among these factors. Our findings highlight the difficulties involved in identifying genes with a functional role in sex determination and gonadal development through expression screening and loss-of-function analyses of individual candidate genes, and may help to explain the paucity of genes in which variations have been found to cause human disorders/differences of sex development.

scholarly journals Expression of steroidogenic factor 1 and Wilms' tumour 1 during early human gonadal development and sex determination

1999 ◽  
Vol 87 (1-2) ◽  
pp. 175-180 ◽  
Author(s):  
N.A. Hanley ◽  
S.G. Ball ◽  
M. Clement-Jones ◽  
D.M. Hagan ◽  
T. Strachan ◽  
...  
Keyword(s):  
Sex Determination ◽  
Gonadal Development ◽  
Wilms Tumour ◽  
Steroidogenic Factor 1 ◽  
Early Human

Major sex-determining genes and the control of sexual dimorphism in Caenorhabditis elegans

Genome ◽  
1989 ◽  
Vol 31 (2) ◽  
pp. 625-637 ◽  
Author(s):  
Jonathan Hodgkin ◽  
Andrew D. Chisholm ◽  
Michael M. Shen
Keyword(s):  
Caenorhabditis Elegans ◽  
Sex Determination ◽  
X Chromosome ◽  
Germ Line ◽  
Cell Lineage ◽  
Regulatory Genes ◽  
Nematode Caenorhabditis Elegans ◽  
X Chromosomes ◽  
The Many ◽  
Lineage Analysis

Sex determination in Caenorhabditis elegans involves a cascade of major regulatory genes connecting the primary sex determining signal, X chromosome dosage, to key switch genes, which in turn direct development along either male or female pathways. Animals with one X chromosome (XO) are male, while animals with two X chromosomes (XX) are hermaphrodite: hermaphrodite development occurs because the action of the regulatory genes is modified in the germ line so that both sperm and oocytes are made inside a completely female soma. The regulatory genes are being examined by both genetic and molecular means. We discuss how these major genes, in particular the last switch gene in the cascade, tra-1, might regulate the many different sex-specific events that occur during the development of the hermaphrodite and of the male.Key words: nematode, Caenorhabditis elegans, sex determination, sexual differentiation, cell lineage analysis.

scholarly journals The role of Caenorhabditis elegans sex-determination homologs, Mi-sdc-1 and Mi-tra-1 in Meloidogyne incognita

2021 ◽  
Author(s):  
Anil Baniya ◽  
Soumi Joseph ◽  
Larry Duncan ◽  
William Crow ◽  
Tesfamariam Mengistu
Keyword(s):  
Caenorhabditis Elegans ◽  
Sex Determination ◽  
Meloidogyne Incognita ◽  
Egg Production ◽  
Target Genes ◽  
Parasitic Nematode ◽  
Plant Parasitic Nematode ◽  
Root Knot Nematode ◽  
Model Free ◽  
Plant Parasitic

AbstractSex determination is a key developmental event in all organisms. The pathway that regulates sexual fate has been well characterized at the molecular level in the model free-living nematode Caenorhabditis elegans. This study aims to gain a preliminary understanding of sex-determining pathways in a plant-parasitic nematode Meloidogyne incognita, and the extent to which the roles of the sex determination genes are conserved in a hermaphrodite species, C. elegans, and plant-parasitic nematode species, M. incognita. In this study, we targeted two sex-determining orthologues, sdc-1 and tra-1 from M. incognita using RNA interference (RNAi). RNAi was performed by soaking second-stage juveniles of M. incognita in a solution containing dsRNA of either Mi-tra-1or Mi-sdc-1 or both. To determine the effect of RNAi of the target genes, the juveniles treated with the dsRNA were inoculated onto a susceptible cultivar of cowpea grown in a nutrient pouch at 28 °C for 5 weeks. The development of the nematodes was analyzed at different time points during the growth period and compared to untreated controls. Our results showed that neither Mi-sdc-1 nor Mi-tra-1 have a significant role in regulating sexual fate in M. incognita. However, the silencing of Mi-sdc-1 significantly delayed maturity to adult females but did not affect egg production in mature females. In contrast, the downregulation of Mi-tra-1 transcript resulted in a significant reduction in egg production in both single and combinatorial RNAi-treated nematodes. Our results indicate that M. incognita may have adopted a divergent function for Mi-sdc-1 and Mi-tra-1distinct from Caenorhabditis spp. However, Mi-tra-1 might have an essential role in female fecundity in M. incognita and is a promising dsRNA target for root-knot nematode (RKN) management using host-delivered RNAi.

scholarly journals Steroidogenic Factor-1 (SF-1)-Driven Differentiation of Murine Embryonic Stem (ES) Cells into a Gonadal Lineage

Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2870-2882 ◽  
Author(s):  
Unmesh Jadhav ◽  
J. Larry Jameson
Keyword(s):  
Target Genes ◽  
De Novo ◽  
Embryoid Body ◽  
Es Cells ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Culture Conditions ◽  
Steroidogenic Factor 1 ◽  
Lineage Differentiation ◽  
And Function

Steroidogenic factor 1 (SF-1) is essential for the development and function of steroidogenic tissues. Stable incorporation of SF-1 into embryonic stem cells (SF-1-ES cells) has been shown to prime the cells for steroidogenesis. When provided with exogenous cholesterol substrate, and after treatment with retinoic acid and cAMP, SF-1-ES cells produce progesterone but do not produce other steroids such as cortisol, estradiol, or testosterone. In this study, we explored culture conditions that optimize SF-1-mediated differentiation of ES cells into defined steroidogenic lineages. When embryoid body formation was used to facilitate cell lineage differentiation, SF-1-ES cells were found to be restricted in their differentiation, with fewer cells entering neuronal pathways and a larger fraction entering the steroidogenic lineage. Among the differentiation protocols tested, leukemia inhibitory factor (LIF) removal, followed by prolonged cAMP treatment was most efficacious for inducing steroidogenesis in SF-1-ES cells. In this protocol, a subset of SF-1-ES cells survives after LIF withdrawal, undergoes morphologic differentiation, and recovers proliferative capacity. These cells are characterized by induction of steroidogenic enzyme genes, use of de novo cholesterol, and production of multiple steroids including estradiol and testosterone. Microarray studies identified additional pathways associated with SF-1 mediated differentiation. Using biotinylated SF-1 in chromatin immunoprecipitation assays, SF-1 was shown to bind directly to multiple target genes, with induction of binding to some targets after steroidogenic treatment. These studies indicate that SF-1 expression, followed by LIF removal and treatment with cAMP drives ES cells into a steroidogenic pathway characteristic of gonadal steroid-producing cells.

scholarly journals Non-Coding Genome, Transcription Factors, and Sex Determination

2021 ◽  
pp. 1-13
Author(s):  
Francis Poulat
Keyword(s):  
Transcription Factors ◽  
Sex Determination ◽  
Target Genes ◽  
Regulatory Elements ◽  
Eukaryotic Cells ◽  
Genomic Profiling ◽  
Binding Motifs ◽  
Male And Female ◽  
Genome Transcription ◽  
Control Complex

In vertebrates, gonadal sex determination is the process by which transcription factors drive the choice between the testicular and ovarian identity of undifferentiated somatic progenitors through activation of 2 different transcriptional programs. Studies in animal models suggest that sex determination always involves sex-specific transcription factors that activate or repress sex-specific genes. These transcription factors control their target genes by recognizing their regulatory elements in the non-coding genome and their binding motifs within their DNA sequence. In the last 20 years, the development of genomic approaches that allow identifying all the genomic targets of a transcription factor in eukaryotic cells gave the opportunity to globally understand the function of the nuclear proteins that control complex genetic programs. Here, the major transcription factors involved in male and female vertebrate sex determination and the genomic profiling data of mouse gonads that contributed to deciphering their transcriptional regulation role will be reviewed.

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