Genetics of sex determination: what can we learn from Drosophila?

Development ◽  
1987 ◽  
Vol 101 (Supplement) ◽  
pp. 17-24
Author(s):  
Rolf Nöthiger ◽  
Monica Steinmann-Zwicky
Keyword(s):  
Molecular Biology ◽  
Sex Determination ◽  
Genetic Control ◽  
Sexual Development ◽  
Sexual Differentiation ◽  
Regulatory Elements ◽  
Negative Control ◽  
Homeotic Genes ◽  
Specific Expression ◽  
X Chromosomes

The combined efforts of genetics, developmental and molecular biology have revealed the principles of genetic control of sexual differentiation in Drosophila. In combination with maternal components, a quantitative chromosomal signal, provided by the ratio of X chromosomes to sets of autosomes (X: A), regulates a key gene (Sxl). The functional state, ON or OFF, of Sxl, via a few subordinate regulatory genes, controls a switch gene (dsx) that can express two mutually exclusive functions, M or F. These serve to repress either the female or the male set of differentiation genes, thus directing the cells either into the male or into the female sexual pathway. Investigations of control genes and their regulation show that they have properties of homeotic genes. Their role is to select one of two alternative developmental programs. Their function, or lack of function, is required throughout development to maintain the cells in their respective sexual pathway. Differentiation genes are under negative control by dsx. We discuss the cis- and tams-regulatory elements that are needed for sex-, tissue- and stage-specific expression of the differentiation genes. A comparison of Drosophila to other organisms such as Caenorhabditis, mammals and other insects indicates similarities that we interpret as evidence for a basically invariant genetic strategy used by various organisms to regulate sexual development.

Clues from other animals and theoretical considerations

Development ◽  
1987 ◽  
Vol 101 (Supplement) ◽  
pp. 3-4
Author(s):  
Anne McLaren
Keyword(s):  
Sex Determination ◽  
Genetic Control ◽  
Y Chromosome ◽  
X Chromosome ◽  
X Chromosomes ◽  
The Third ◽  
Mouse Species ◽  
Primary Male ◽  
Theoretical Considerations ◽  
State Of Activity

In the first two papers of this volume, the genetic control of sex determination in Caenorhabditis and Drosophila is reviewed by Hodgkin and by Nöthiger & Steinmarin-Zwicky, respectively. Sex determination in both cases depends on the ratio of X chromosomes to autosomes, which acts as a signal to a cascade of règulatory genes located either on autosomes or on the X chromosome. The state of activity of the last gene in the sequence determines phenotypic sex. In the third paper, Erickson & Tres describe the structure of the mouse Y chromosome and the polymorphisms that have been detected in different mouse species and strains. As in all mammals, the Y carries the primary male-determining locus; autosomal genes may also be involved in sex determination, but they must act down-stream from the Y-linked locus.

scholarly journals Distinct developmental mechanisms influence sexual dimorphisms in the milkweed bug Oncopeltus fasciatus

2021 ◽  
Author(s):  
Josefine Just ◽  
Mara Laslo ◽  
Ye Jin Lee ◽  
Michael C Yarnell ◽  
Zhuofan Zhang ◽  
...  
Keyword(s):  
Sex Determination ◽  
The Body ◽  
Oncopeltus Fasciatus ◽  
Sexually Dimorphic ◽  
Specific Expression ◽  
X Chromosomes ◽  
Milkweed Bug ◽  
Multiple Transcripts ◽  
Complex Protein ◽  
Male Specific

Sexual dimorphism is a common feature of animals. Sex determination mechanisms vary widely among species and evolve rapidly. Until recently studies have found consistent mechanisms across the body of each individual determine female or male dimorphic body structures. In sexually dimorphic cells throughout the body of Drosophila, the relative dosage of autosomes and X chromosomes leads indirectly to alternatively spliced transcripts from the gene doublesex. The female Dsx isoform interacts with the mediator complex protein encoded by intersex to activate female development in flies. In males the transcription factor encoded by fruitless promotes male-specific behavior. In the milkweed bug Oncopeltus fasciatus, we find a requirement for different combinations of these genes during development of distinct dimorphic structures, within the same sex, suggesting a previously unappreciated level of diversity in sex determination. While intersex and fruitless are structurally conserved, doublesex has a history of duplication and divergence among Paraneoptera. Three doublesex paralogs in O. fasciatus produce multiple transcripts with sex- and tissue-specific expression. intersex and fruitless are expressed across the body, in females and males. RNA interference reveals only one doublesex paralog functions in somatic sex determination. Knockdown of doublesex and fruitless produces intersex phenotypic conditions in two sexually dimorphic structures: genitalia and abdominal sternites. In contrast, intersex is required for dimorphic development of female and male genitalia, but not for sternite dimorphism. These results reveal sex determination roles for intersex and fruitless distinct from their orthologs in other insects. Our results illuminate a novel form of developmental diversity in insect sex determination.

scholarly journals The Primary Sex Determination Signal of Caenorhabditis elegans

Genetics ◽  
1999 ◽  
Vol 152 (3) ◽  
pp. 999-1015 ◽  
Author(s):  
Ilil Carmi ◽  
Barbara J Meyer
Keyword(s):  
Caenorhabditis Elegans ◽  
Sex Determination ◽  
Counting Process ◽  
Rna Binding ◽  
Nuclear Hormone Receptor ◽  
Chromosome Counting ◽  
Specific Expression ◽  
X Chromosomes ◽  
Signal Element ◽  
Complete Transformation

AbstractAn X chromosome counting process determines sex in Caenorhabditis elegans. The dose of X chromosomes is translated into sexual fate by a set of X-linked genes that together control the activity of the sex-determination and dosage-compensation switch gene, xol-1. The double dose of X elements in XX animals represses xol-1 expression, promoting the hermaphrodite fate, while the single dose of X elements in XO animals permits high xol-1 expression, promoting the male fate. Previous work has revealed at least four signal elements that repress xol-1 expression at two levels, transcriptional and post-transcriptional. The two molecularly characterized elements include an RNA binding protein and a nuclear hormone receptor homolog. Here we explore the roles of the two mechanisms of xol-1 repression and further investigate how the combined dose of X signal elements ensures correct, sex-specific expression of xol-1. By studying the effects of increases and decreases in X signal element dose on male and hermaphrodite fate, we demonstrate that signal elements repress xol-1 cumulatively, such that full repression of xol-1 in XX animals results from the combined effect of individual elements. Complete transformation from the hermaphrodite to the male fate requires a decrease in the dose of all four elements, from two copies to one. We show that both mechanisms of xol-1 repression are essential and act synergistically to keep xol-1 levels low in XX animals. However, increasing repression by one mechanism can compensate for loss of the other, demonstrating that each mechanism can exert significant xol-1 repression on its own. Finally, we present evidence suggesting that xol-1 activity can be set at intermediate levels in response to an intermediate X signal.

scholarly journals sisterless A is required for the activation of Sex lethal in the germline

2019 ◽  
Author(s):  
Raghav Goyal ◽  
Ellen Baxter ◽  
Mark Van Doren
Keyword(s):  
Sex Determination ◽  
X Chromosome ◽  
Germ Cells ◽  
Specific Expression ◽  
Male Germ Cells ◽  
X Chromosomes ◽  
Dna Elements ◽  
Sex Lethal ◽  
Female Specific ◽  
Necessary And Sufficient

ABSTRACTIn Drosophila, sex determination in somatic cells has been well-studied and is under the control of the switch gene Sex lethal (Sxl), which is activated in females by the presence of two X chromosomes. Though sex determination is regulated differently in the germline versus the soma, Sxl is also necessary and sufficient for the female identity in germ cells. Loss of Sxl function in the germline results in ovarian germline tumors, a characteristic of male germ cells developing in a female soma. Further, XY (male) germ cells expressing Sxl are able to produce eggs when transplanted into XX (female) somatic gonads, demonstrating that Sxl is also sufficient for female sexual identity in the germline. As in the soma, the presence of two X chromosomes is sufficient to activate Sxl in the germline, but the mechanism for “counting” X chromosomes in the germline is thought to be different from the soma. Here we have explored this mechanism at both cis- and trans-levels. Our data support the model that the Sxl “establishment” promoter (SxlPE) is activated in a female-specific manner in the germline, as in the soma, but that the timing of SxlPE activation, and the DNA elements that regulate SxlPE are different from those in the soma. Nevertheless, we find that the X chromosome-encoded gene sisterless A (sisA), which helps activate Sxl in the soma, is also essential for Sxl activation in the germline. Loss of sisA function leads to loss of Sxl expression in the germline, and to ovarian tumors and germline loss. These defects can be rescued by the expression of Sxl, demonstrating that sisA lies upstream of Sxl in germline sex determination. We conclude that sisA acts as an X chromosome counting element in both the soma and the germline, but that additional factors that ensure robust, female-specific expression of Sxl in the germline remain to be discovered.

scholarly journals Hemimetabolous insects elucidate the origin of sexual development via alternative splicing

2019 ◽  
Author(s):  
Judith Wexler ◽  
Emily K. Delaney ◽  
Xavier Belles ◽  
Coby Schal ◽  
Ayako Wada-Katsumata ◽  
...  
Keyword(s):  
Sexual Development ◽  
Sexual Differentiation ◽  
Rna Splicing ◽  
Molecular Mechanisms ◽  
Protein Isoforms ◽  
Splicing Factor ◽  
Specific Expression ◽  
Male And Female ◽  
Pediculus Humanus ◽  
Alternatively Spliced

ABSTRACTInsects are the only animals in which sexual differentiation is controlled by sex-specific RNA splicing. Thedoublesex(dsx) transcription factor produces distinct male and female protein isoforms (DsxM and DsxF) under the control of the RNA splicing factortransformer(tra).traitself is also alternatively spliced so that a functional Tra protein is only present in females; thus, DsxM is produced by default, while DsxF expression requires Tra. The sex-specific Dsx isoforms are essential for both male and female sexual differentiation. This pathway is profoundly different from the molecular mechanisms that control sex-specific development in other animal groups. In animals as different as vertebrates, nematodes, and crustaceans, sexual differentiation involves male-specific transcription ofdsx-related transcription factors that are not alternatively spliced and play no role in female sexual development. To understand how the unique splicing-based mode of sexual differentiation found in insects evolved from a more ancestral transcription-based mechanism, we examineddsxandtraexpression in three basal, hemimetabolous insect orders. We find that functional Tra protein is limited to females in the kissing bugRhodnius prolixus(Hemiptera), but is present in both sexes in the lousePediculus humanus(Phthiraptera) and the cockroachBlattella germanica(Blattodea). Although alternatively spliceddsxisoforms are seen in all these insects, they are sex-specific in the cockroach and the kissing bug but not in the louse. InB. germanica, RNAi experiments show thatdsxis necessary for male, but not female, sexual differentiation, whiletracontrols female development via adsx-independent pathway. Our results suggest that the distinctive insect mechanism based on thetra-dsxsplicing cascade evolved in a gradual, mosaic process: sex-specific splicing ofdsxpredates its role in female sexual differentiation, while the role oftrain regulatingdsxsplicing and in sexual development more generally predates sex-specific expression of the Tra protein. We present a model where the canonicaltra-dsxaxis originated via merger between expandingdsxfunction (from males to both sexes) and narrowingtrafunction (from a general splicing factor to the dedicated regulator ofdsx).

Mab-3 is a direct tra-1 target gene regulating diverse aspects of C. elegans male sexual development and behavior

Development ◽  
2000 ◽  
Vol 127 (20) ◽  
pp. 4469-4480 ◽  
Author(s):  
W. Yi ◽  
J.M. Ross ◽  
D. Zarkower
Keyword(s):  
Transcription Factor ◽  
Sex Determination ◽  
Sexual Development ◽  
Sexual Differentiation ◽  
Sense Organ ◽  
Yolk Protein ◽  
Bhlh Transcription Factor ◽  
Organ Differentiation ◽  
And Behavior ◽  
Protein Transcription

Sex determination is controlled by global regulatory genes, such as tra-1 in Caenorhabditis elegans, Sex lethal in Drosophila, or Sry in mammals. How these genes coordinate sexual differentiation throughout the body is a key unanswered question. tra-1 encodes a zinc finger transcription factor, TRA-1A, that regulates, directly or indirectly, all genes required for sexual development. mab-3 (male abnormal 3), acts downstream of tra-1 and is known to be required for sexual differentiation of at least two tissues. mab-3 directly regulates yolk protein transcription in the intestine and specifies male sense organ differentiation in the nervous system. It encodes a transcription factor related to the products of the Drosophila sexual regulator doublesex (dsx), which also regulates yolk protein transcription and male sense-organ differentiation. The similarities between mab-3 and dsx led us to suggest that some aspects of sex determination may be evolutionarily conserved. Here we find that mab-3 is also required for expression of male-specific genes in sensory neurons of the head and tail and for male interaction with hermaphrodites. These roles in male development and behavior suggest further functional similarity to dsx. In male sensory ray differentiation we find that MAB-3 acts synergistically with LIN-32, a neurogenic bHLH transcription factor. Expression of LIN-32 is spatially restricted by the combined action of the Hox gene mab-5 and the hairy homolog lin-22, while MAB-3 is expressed throughout the lateral hypodermis. Finally, we find that mab-3 transcription is directly regulated in the intestine by TRA-1A, providing a molecular link between the global regulatory pathway and terminal sexual differentiation.

scholarly journals Evolutionary conservation of regulatory strategies for the sex determination factor transformer-2.

1997 ◽  
Vol 17 (5) ◽  
pp. 2908-2919 ◽  
Author(s):  
D Chandler ◽  
M E McGuffin ◽  
J Piskur ◽  
J Yao ◽  
B S Baker ◽  
...  
Keyword(s):  
Sex Determination ◽  
Sexual Differentiation ◽  
Germ Line ◽  
Drosophila Virilis ◽  
Protein Isoforms ◽  
Normal Female ◽  
Specific Expression ◽  
Regulatory Pathways ◽  
Alternative Processing ◽  
And Function

Sex determination in Drosophila melanogaster is regulated by a cascade of splicing factors which direct the sex-specific expression of gene products needed for male and female differentiation. The splicing factor TRA-2 affects sex-specific splicing of multiple pre-mRNAs involved in sexual differentiation. The tra-2 gene itself expresses a complex set of mRNAs generated through alternative processing that collectively encode three distinct protein isoforms. The expression of these isoforms differs in the soma and germ line. In the male germ line the ratio of two isoforms present is governed by autoregulation of splicing. However, the functional significance of multiple TRA-2 isoforms has remained uncertain. Here we have examined whether the structure, function, and regulation of tra-2 are conserved in Drosophila virilis, a species diverged from D. melanogaster by over 60 million years. We find that the D. virilis homolog of tra-2 produces alternatively spliced RNAs encoding a set of protein isoforms analogous to those found in D. melanogaster. When introduced into the genome of D. melanogaster, this homolog can functionally replace the endogenous tra-2 gene for both normal female sexual differentiation and spermatogenesis. Examination of alternative mRNAs produced in D. virilis testes suggests that germ line-specific autoregulation of tra-2 function is accomplished by a strategy similar to that used in D. melanogaster. The similarity in structure and function of the tra-2 genes in these divergent Drosophila species supports the idea that sexual differentiation in D. melanogaster and D. virilis is accomplished under the control of similar regulatory pathways.

Primary Genetic-Control of Sexual-Differentiation in Marsupials

1989 ◽  
Vol 37 (3) ◽  
pp. 443 ◽  
Author(s):  
G Shaw ◽  
MB Renfree ◽  
RV Short
Keyword(s):  
Genetic Control ◽  
Y Chromosome ◽  
X Chromosome ◽  
Sexual Differentiation ◽  
Hormonal Control ◽  
Sexually Dimorphic ◽  
Processus Vaginalis ◽  
X Chromosomes

Marsupials, like eutherians, normally require the presence of a Y chromosome for testicular formation. However some sexually dimorphic characters such as the scrotum, mammary anlagen, gubernaculum and processus vaginalis appear to be under direct genetic rather than secondary hormonal control. Scrota1 development occurs where only a single X chromosome is functional, whilst two X chromosomes are necessary for pouch formation.

scholarly journals Evolution of sexual development and sexual dimorphism in insects

2021 ◽  
Author(s):  
Ben Hopkins ◽  
Artyom Kopp
Keyword(s):  
Sexual Dimorphism ◽  
Sex Determination ◽  
Sexual Development ◽  
Animal Species ◽  
Molecular Genetic ◽  
Comparative Perspective ◽  
Specific Expression ◽  
Environmental Signals ◽  
Males And Females ◽  
Insect Sex

Most animal species consist of two distinct sexes. At the morphological, physiological, and behavioural levels the differences between males and females are numerous and dramatic, yet at the genomic level they are often slight or absent. This disconnect is overcome because simple genetic differences or environmental signals are able to direct the sex-specific expression of a shared genome. A canonical picture of how this process works in insects emerged from decades of work on Drosophila. But recent years have seen an explosion of molecular-genetic and developmental work on a broad range of insects. Drawing these studies together, we describe the evolution of sexual dimorphism from a comparative perspective and argue that insect sex determination and differentiation systems are composites of rapidly evolving and highly conserved elements.

scholarly journals CRISPR/Cas9-mediated mosaic mutation of SRY gene induces hermaphroditism in rabbits

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Yuning Song ◽  
Yuanyuan Xu ◽  
Mingming Liang ◽  
Yuxin Zhang ◽  
Mao Chen ◽  
...  
Keyword(s):  
Sex Determination ◽  
Sexual Development ◽  
Sexual Differentiation ◽  
Rabbit Model ◽  
Gonad Development ◽  
High Mobility ◽  
Testicular Tissue ◽  
Spermatogenic Cells ◽  
Sry Gene ◽  
Male Sex

Hermaphroditism is a rare disorder that affects sexual development, resulting in individuals with both male and female sexual organs. Hermaphroditism is caused by anomalies in genes regulating sex determination, gonad development, or expression of hormones and their receptors during embryonic development during sexual differentiation. SRY is a sex-determination gene on the Y chromosome that is responsible for initiating male sex determination in mammals. In this study, we introduced CRISPR/Cas9-mediated mutations in the high-mobility-group (HMG) region of the rabbit SRY. As expected, SRY-mutant chimeric rabbits were diagnosed with hermaphroditism, characterized by possessing ovotestis, testis, ovary and uterus simultaneously. Histopathology analysis revealed that the testicular tissue was immature and lacked spermatogenic cells, while the ovarian portion appeared normal and displayed follicles at different stages. This is the first report of a rabbit hermaphroditism model generated by the CRISPR/Cas9 system. This novel rabbit model could advance our understanding of the pathogenesis of hermaphroditism, and identify novel therapies for human clinical treatment of hermaphroditism.

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