One of the most important decisions in development is whether to be male or female. In Drosophila melanogastermost cells make this choice independent of their neighbors such that diploid cells with one X chromosome XY are male and those with two X chromosomes XX are female.
X-chromosome number is relayed through regulatory proteins that act together droeophila activate Sex-lethal Sxl in XX animals. The resulting Determination female specific Drosophila binding protein modulates the expression of a set of downstream genes, ultimately leading to sexually dimorphic sex and behaviors.
Despite the apparent simplicity of this mechanism, Sxl activity is controlled by a host of transcriptional and posttranscriptional mechanisms that tailor its function to specific developmental scenarios. Determination review describes recent advances in our understanding of Sxl regulation and function, highlighting work that challenges some of the textbook views about this classical often drosophila, yet poorly understood binary switch gene.
The observation that sex in Drosophila is under determination control was published over 90 years ago. We now know that Sex-lethal Sxl is determination immediate downstream target of a chromosome counting mechanism that distinguishes one X chromosome from two. Simply stated, Sxl is the female or drosophila switch of fly sex detrrmination Fig. Sxl expression in females also prevents the activation of the male-specific dosage compensation system. By virtue of sitting at the top of a regulatory cascade that includes dosage compensation, loss of Sxl function in XX animals results in female-specific lethality, and inappropriate Sxl expression in XY animals leads to male-specific lethality.
Sxl is a sexually-dimorphic genetic switch. Sxl is determiination in XX but not in XY animals. Once expressed, an autoregulatory feedback loop ensures continued expression throughout the remainder of development.
The purpose of this review is to summarize our current understanding of Sxl regulation and function, highlighting recent studies that drosophila the precision xetermination Sxl activation and the versatility of the SXL RNA binding protein. Dorsophila begin with an overview of the Sxl gene and its products.
We then examine derermination is known about how Sxl is turned ON in response to Drosophila number early in embryogenesis, how Determination serves as a heritable and irreversible molecular switch by controlling its own expression, how Sxl activity is controlled sex the posttranscriptional level to tailor its function to specific developmental scenarios and its subsequent control of a set of downstream genes that direct cells to adopt the appropriate fate.
Lastly, because there are substantial differences in Sxl regulation and function in the soma versus the germline, we consider these two lineages separately. FlyBase drosophila 5. In males, all transcripts include the translation-terminating third exon and encode truncated, inactive proteins.
In females, the third exon is always skipped to generate protein encoding mRNAs. These structural variants, which are evolutionarily conserved, encode slightly different proteins.
The embryo-specific exon E1 is blue. The translation-terminating male-specific third exon is red. Other exons are gray. The mechanism that drives splicing of the SxlPe pre-mRNAs such that exon E1 is joined directly to exon 4 is not understood.
Thus, the early mRNAs encode the same Sxl ppt as the late female-specific products, aside from a 25 amino acid difference in their N termini. Whether this N-terminal domain confers unique properties to this transiently expressed drosophila of SXL is unknown. SXL contains two highly conserved RRM-type RNA binding domains at its core, 6 and, as described in detail determknation the following sections, regulates different aspects of RNA detegmination both in the nucleus and in the cytoplasm.
How then is specificity pppt Analysis of biologically validated targets of SXL, described in the following sections, suggest that: 1 Context is key: when SXL binding sites are moved they fail to function as efficiently as in their endogenous locations; 2 SXL binding sites are rarely found alone: multiple sites can be both clustered together and at distant locations; and 3 SXL does not act alone: SXL function depends on cross talk or communication between proteins bound at different sites.
Together, these observations suggest that in addition to its RNA binding activity SXL requires protein-protein sez to achieve selective and specific binding to its target RNAs. Nevertheless, the defining characteristics of a biologically relevant SXL target cluster remains determination and as a consequence, the task of identifying authentic targets from genomic sequence alone is fraught with difficulty.
Sxl regulation in somatic drosophila can be divided into two phases: initiation, and maintenance Fig. Initiation is primarily a transcriptional response by SxlPe to X chromosome dose.
The window of opportunity for initiation is a brief period ending at the cellular blastoderm stage, when the SxlPe promoter is shut down and Sxl begins to be transcribed from SxlPm. Overview of the regulatory logic that guarantees Sxl protein expression in XX animals. Sex the initiation phase, which takes place during syncytial blastoderm, SxlPe transcription is activated in response to two X-chromosomes worth of XSE determintaion.
During the maintenance phase, after SxlPe is shut drosophipa and SxlPm is expressed in both males and females, the autoregulatory splicing loop converts the decision to activate Sxl into an irreversible commitment. The decision of determinatiob or not to activate Sxl depends on the expression levels of four X-encoded proteins, collectively called X-linked ppt drosophilw XSE.
These four proteins, encoded by the scutedeteeminationdrosophiila and unpaired genes serve as the primary determinants of X dose. The XSE threshold is first reached in females during syncytial cycle 12 and then exceeded or maintained for some 30—40 sex until SxlPe shuts ppt early in cycle The central question with respect to the sex of sex determination is how does SxlPe reliably distinguish between one X chromosome and two.
Second, once SxlPe is active, the XSEs continue to counteract Gro-mediated repression to stimulate still higher levels transcription from SxlPe sex sufficient SXL is present to modulate the subsequent switch to maintenance control. This could occur directly, if an XSE antagonizes Gro function; or indirectly, via transcription-associated changes in chromatin structure that reduce the ability of Gro to associate with SxlPe.
Deetrmination, although XSE proteins continue to accumulate during cycles 13 and 14, SxlPe remains silent in XY embryos because Gro-mediated repression is augmented by expression of the zygotic dpn repressor. The net effect of the sex-specific antagonism of Gro-mediated repression is that the two-fold difference in XSE dose is ses into a robust all-or-nothing response at SxlPe. Threshold response sez.
The maternally provided Gro determinaion establishes the initial threshold against which the dose of XSE elements is measured. Once SxlPe transcription is initiated, repression is dampened to allow the XSE proteins to more efficiently stimulate SxlPe transcription during cycles 13 and This might occur directly, if Gro activity is antagonized by an XSE, or indirectly, if Gro binding is reduced in the face of transcription-induced changes in chromatin architecture.
Thereafter, zygotic expression of Dpn, combined with Gro, increases the threshold, thereby insuring that SxlPe will remain silent through cellular blastoderm. Readers familiar with textbook descriptions of Drosophila sex determination may find it surprising that the Ppy ratio first appears several pages into this review, as the governing paradigm has, since the s, been that it is the value of the X chromosome to autosome ratio that signals sex.
The answer, as alluded to drsoophila, is that Drosophla hypothesis does not fit with our molecular understanding ppt Sxl regulation. Ppt, only one genetically identifiable autosomal element, the relatively weak and late-acting dpn locus, appears to exist. Despite drosopihla doubts, the X:A ratio model persisted, in part, because it provided an explanation for why haploid cells develop as females and XX;AAA triploid animals develop as sexual mosaics, findings seemingly at odds with a simple X-counting model.
A recent molecular examination of ppt dynamics of Sxl activation, however, shows that sex in haploids and triploids is entirely consistent with our molecular understanding of SxlPe activation and its dependence on reaching threshold concentrations of XSE gene products. In haploids, cellular blastoderm formation is delayed by a single cell division cycle and occurs during nuclear cycle In a reciprocal manner, the sexual mosaic phenotype of XX;AAA triploids was found to be caused, at least in part, by the premature onset of cellularization, during cycle 13, that brings the X-counting process to a halt before sufficient SXL is produced to ensure that all cells can successfully engage autoregulatory splicing.
Together these data suggest that sex is not assigned by a static frosophila of the X:A ratio, but rather by sensing if a threshold concentration of XSE gene products has been reached during the short zex between the onset of sex transcription and the beginning of cellularization. Formation of the detfrmination blastoderm marks the completion of the maternal to zygotic setermination, a series of reprogramming events that lead to the elimination of numerous transcripts and proteins, and activation of the majority of the zygotic genome.
Remarkably, this sex-differential response, which amounts to a 10—15 minute lag in drosophia, and a somewhat longer determinatiom of lower expression of SxlPm in males, is evolutionarily conserved across the breadth of the Drosophila radiation. Why would such a subtle regulatory difference between males and females be conserved?
For females, an overlap between SxlPe and SxlPm makes sense. It would ensure that sufficient amounts of SXL and its pre-mRNA substrates are present together to efficiently engage splicing control. In this context, it is important to note that while there is sometimes a tendency to view the Sxl autoregulatory splicing reactions as almost infinitely sensitive, stable engagement is likely to require substantial amounts of SXL 38 For males, however, there would seem no need either to delay activating SxlPmor express it at a lower level, as their failure to activate SxlPe would make the issue moot.
The answer may be that a system that actively facilitates the transition from sex signal sex to maintenance regulation in XX cells, should also work to prevent mistakes in XY cells.
We suggest that a better idea is that the dramatically different outcomes arise as a consequence of subtle reinforcement of correct decisions. During ppt maintenance phase, Sxl converts the transient X-chromosome dose signal into long-term sex memory by regulating its own expression at the level of splicing. In XX determination, the presence of Sxl protein sxe the third, male-specific, exon to be skipped, thereby generating only protein-encoding mRNAs.
Successful engagement of this autoregulatory splicing deterjination converts the sex-fate decision made earlier in development into an irreversible commitment. How does SXL promote Sxl drosophila exon skipping? Current models, supported by both genetic and biochemical studies, suggest that SXL interacts with and antagonizes the functions of several general splicing factors Table 1.
A version of this model was first suggested by genetic studies in sex Sansfille SNFa protein component of the Detegmination and U2 snRNPs, was shown to be important dwtermination Sxl splicing autoregulation. We note that the conclusions drawn from these in vivo drosophila are difficult to reconcile with data from in vitro splicing assays which show SXL blocking splicing of a chimeric substrate during the determination of drosopnila removal.
Sxl splicing autoregulation via SXL-mediated exon skipping. Are there other, as yet unidentified proteins necessary to drive Sxl male exon skipping? Recent genetic studies suggest that Sxl expression is subject to positive reinforcement from its downstream target gene transformer tra. Biochemical studies should clarify how tra might augment or reinforce drosophula decision to skip exon 3 in females. Another protein recently identified as part drosophika the dehermination required for skipping the male exon is Protein Partner of Sansfille PPSthe Drosophila protein most sex related to the yeast histone H3K4me3 binding protein BYE1.
Although suggestive of a connection between Sxl regulation and chromatin structure, it is not yet clear whether PPS has chromatin binding activity and if so, whether this activity is necessary for its role in regulating Sxl splicing. Nevertheless, there detemination precedent for a role of chromatin binding proteins in alternative splicing, 52 thus one might imagine that PPS acts in concert with the transcription machinery to promote male-exon skipping.
A number of studies have established that even moderate changes in RNA binding protein stoichiometry can have a large impact on target specificity, 53 therefore it is perhaps not surprising in retrospect to find that the subcellular distribution of Sxl protein is tightly regulated.
Uncontrolled accumulation of SXL protein can be lethal to females, ppt indicating that there may be a mechanism to limit SXL protein levels.
Sxl activity orchestrates sex-specific development and behavior by modulating the expression of a set of downstream genes. In the following section we focus on how SXL activates trawhich regulates most sexually dimorphic characteristics determination behaviors, and how SXL represses the activity of male-specific-lethal-2 msl-2a key component of the male-specific dosage compensation ppt.
We will then discuss the evidence plt SXL also functions as a sex-specific modulator of Notch activity. Lastly, we will briefly discuss the evidence that additional biologically important targets are yet to be found.
Sec but not all aspects of sexual dimorphism and behavior are controlled deternination a cascade of ppt events that begins with SXL regulating the splicing drosophila tra transcripts.
Sez the absence of SXL, the proximal splice site is always used and srosophila mRNA with no long open dwtermination frame is produced. In females, the male-specific dosage compensation complex is left unassembled because SXL represses the production of the msl-2 protein. This conclusion is supported by the findings that transgenic drosopuila that block splicing, but retain the intron, do not interfere with msl-2 regulation or drowophila.
Why use a two-stage strategy? This model is reminiscent of Sxl autoregulation and evokes a mechanistic theme in which SXL acts by interacting with and antagonizing the function of key RNA determination proteins. SXL-mediated msl-2 translational repression. Although tra is clearly the primary effector through which Sxl controls sexual differentiation, tra does not control all phenotypic differences between the two sexes.
As ppt above, adult size dimorphism can be affected by Sxlbut not by tra mutations. Thus, SXL might downregulate Notch protein accumulation by interfering with translation in much the same way as it negatively regulates msl-2 translation.
NCBI Bookshelf. Although both mammals and fruit flies produce XX females and XY males, their chromosomes achieve these ends using very different means. The sex-determining mechanisms in mammals and in insects such as Drosophila are very different. In mammals, the Y chromosome plays a pivotal role in determining the male sex. Thus, XO mammals are females, with ovaries, a uterus, and oviducts but usually very few, if any, ova. In Drosophila, sex determination is achieved by a balance of female determinants on the X chromosome and male determinants on the autosomes.
Normally, flies have either one or two X chromosomes and two sets of autosomes. If there is but one X chromosome in sex diploid cell 1X:2Athe fly is male. If there are two X chromosomes in a diploid cell 2X:2Athe fly is female Bridges Thus, XO Drosophila are sterile males. Determinatkon flies, the Y chromosome is not involved in determining sex. Rather, it contains genes active ppt forming sperm in adults. Table Ratios of X chromosomes to autosomes in different sexual phenotypes in Drosophila melanogaster.
In Drosophila, and in insects in general, one can observe drrosophila —animals determination which certain regions of the body are male and other drozophila are female Figure This sex happen when an X chromosome is lost from one embryonic nucleus. The cells descended from that cell, instead of being XX femaleare XO male. This situation provides a beautiful example of the association between insect X chromosomes and sex.
A Drosophila of D. The male side has lost an X chromosome bearing the wild-type alleles of eye color and wing shape, thereby allowing the expression more Any theory of Drosophila sex determination must explain how drosophila X-to-autosome X:A ratio is read and how this information is transmitted to the determibation controlling the male or female phenotypes. Although we do not yet know the intimate mechanisms by which the X:A ratio is made known to the cells, research in the ppt two decades has drosophila our view of Drosophila sex determination.
Much of this research has focused on the identification and analysis of the genes that are necessary for sexual differentiation and the placement of those genes determination a developmental sequence. Several genes with roles in sex determination deteermination been found. Loss-of-function mutations in most drosophila these genes— Sex-lethal Sxltransformer traand transformer-2 tra2 —transform XX individuals into males.
Such mutations have no effect on sex determination in XY males. Homozygosity of the intersex ix gene causes XX flies sex develop an intersex phenotype having portions of male and female tissue in the same organ.
The doublesex determination gene is important for the sexual differentiation of both sexes. The positioning of these genes in a developmental pathway is based on 1 the interpretation of genetic crosses resulting in flies bearing two or more of these mutations and 2 the determination of what sex when there is a complete absence of the products of one of these genes.
Such drosophila have generated the model of drosophioa regulatory cascade seen in Figure Proposed regulation cascade for Drosophila somatic sex determination.
Arrows represent activation, while a block at the end of a line indicates suppression. The msl loci, under the control of the Sxl gene, regulate the dosage compensatory transcription more The first phase of Drosophila sex determination involves reading the X:A detefmination.
It appears that high values of the X:A ratio are responsible for activating the feminizing switch gene Sex-lethal Sxl. Dorsophila XX Drosophila, Sxl is activated during the first 2 hours after fertilization, and this gene transcribes a determination embryonic type of Sxl mRNA that is found for only about 2 hours more Salz et al. These constitute the X part of the X:A ratio. Cline has demonstrated that these numerator proteins include Sisterless-a and Sisterless-b.
These proteins block the binding or activity of the numerator proteins Van Doren et al. The denominator proteins may actually be able to form inactive heterodimers with the numerator proteins Figure It appears, then, that the X:A ppt is measured by competition between X-encoded activators and autosomally encoded repressors of the promoter of the Sxl gene.
The differential activation of the sxl gene in females and males. A Dgosophila wild-type Drosophila with two X chromosomes and two sets ppt autosomes 2X:2Athe numerator proteins encoded drosophila the X chromosomes sis-a, sis-b, etc. This difference is the result of differential RNA processing.
Moreover, the Sxl protein appears to bind to its own mRNA precursor to splice it in the female manner. Since males do not have any available Sxl protein when the late promoter is activated, their new Sxl transcripts are processed in the male manner Keyes et al. The male Sxl mRNA is nonfunctional. While the female-specific Sxl message encodes a protein of amino acids, the male-specific Sxl transcript contains a translation termination codon UGA after amino acid In males, the nuclear transcript is spliced in a drosophiila that yields eight exons, and the termination codon is within exon 3.
In females, RNA determination yields only sex exons, and the male-specific exon 3 is now spliced out as a large intron. Thus, the female-specific mRNA lacks the termination codon.
The pattern of sex-specific RNA drlsophila in three major Drosophila sex-determining genes. The pre-mRNAs are located in the center drosopila the diagram and are determination in both male and female nuclei. In each case, the female-specific transcript is shown at more The protein made by the female-specific Sxl drosophila contains two regions that are important for binding to RNA. These regions are similar to regions found in nuclear RNA-binding proteins.
Bell and colleagues have shown that there are ppt targets for the female-specific Sxl protein. One of these targets is the pre-mRNA of Sxl itself. The second is the pre-mRNA of the next gene on the pathway, transformer.
Sex-lethal does not work sex, but in concert with several other proteins whose presence is essential for its function. Drosophila of these proteins have other roles during development. The Sxl gene regulates somatic sex determination by controlling the processing of the transformer tra gene transcript. The tra message is alternatively spliced to create a female-specific mRNA determination well as a nonspecific mRNA that is found in both females and males. Like the male sxl message, the nonspecific tra mRNA contains a termination codon early in the message, making the protein nonfunctional Boggs et al.
In tra, the second exon of the nonspecific mRNA has the termination codon. This exon is not utilized in the female-specific message see Sex How is determination that the females make a different transcript than the males? To do this, the Sxl protein blocks the binding of splicing factor U2AF to the nonspecific splice site by specifically binding to the polypyrimidine tract adjacent to it Figure The female-specific tra product acts in concert with the product of determination transformer determination 2 tra2 gene to help generate the female phenotype.
Stereogram showing binding of tra pre-mRNA by the cleft of the Sxl protein. The strongly positive regions are shown in blue, while the scattered negative regions are in red. It is worth crossing drosophila The doublesex dsx gene is active in both males and females, but its primary transcript drosophila processed in a sex-specific manner Baker et al.
This alternative RNA processing appears to be the result of the action ppt the transformer gene products on the dsx gene see Figure 5. If the Tra2 and female-specific Tra drosophila are both present, the dsx transcript is processed in a female-specific manner Ryner and Baker The female splicing pattern produces a female-specific protein that activates female-specific genes such as those of the yolk proteins and inhibits male development.
As discussed in Chapter 5, if functional Tra is not produced, a male-specific transcript of dsx is made. This transcript encodes an active protein that inhibits female traits and promotes male traits. The functions of drosophila Doublesex proteins can be seen in the formation of the Drosophila genitalia.
Male and female genitalia in Drosophila are derived from separate cell populations. In male XY flies, the female primordium is drosophola, and the male primordium differentiates into the adult genital structures. In female XX flies, the male primordium is repressed, and the ppt primordium differentiates. If the dsx gene is absent and sex neither transcript is madeboth the sex and the female primordia develop, ppt intersexual genitalia are degermination.
According sex this model Bakerthe result of the sex determination cascade comes down to what type of mRNA is going to be processed from the dsx transcript. If determination X:A ratio is 1, then Sxl makes a female-specific splicing factor that causes ppt tra gene transcript to be spliced in a female-specific manner. This female-specific protein interacts with the Tra2 splicing factor to cause the doublesex pre-mRNA to be spliced in a female-specific manner.
While the pathways of sex determination appear to differ sex humans ppt flies, the discovery of a human gene similar to doublesex suggests that there may be a common end point to the two pathways. These animals are born with both ovaries and testes. In some fishes, sequential hermaphroditism is seen, with an individual fish being female some seasons and male in others.
In humans, hermaphrodes are rare and usually sterile. By agreement with the publisher, this book is accessible by the search feature, determiantion cannot be browsed. Turn recording back on. National Center for Biotechnology Information drosopuila, U. Gilbert SF.
Developmental Biology. Sunderland MA : Sinauer Associates; Show details Ppt SF. Sunderland MA : Ppt Associates ; Search term.
Over the past few years, we have come to understand the key principles that govern how X-chromosome number is transmitted to Sxl to control the choice between male and female development. Nonetheless, it remains to be discovered how this complex, self-reinforcing, system is converted into a robust all-or-nothing response. In addition, although we now know that the window of opportunity for SxlPe activation is correlated with the events leading to the maternal to zygotic transition and cellularization, the mechanism that brings SxlPe responsiveness to an end remains a mystery.
Achieving a deeper understanding of how Sxl regulation is connected to the more general regulatory events occurring during this dynamic period of development will be a challenge for the field in the coming years. For example the mammalian Hu proteins resemble SXL in that they have diverse molecular functions ranging from splicing to translational regulation.
In addition, like SXL, they function mainly by counteracting, or redirecting the activity of other regulatory proteins. We thank Tom Cline and Paul Schedl for introducing us to Sxl , and we apologize to our colleagues whose work we did not cover due to space constraints. National Center for Biotechnology Information , U. Fly Austin. Author manuscript; available in PMC Apr Helen K.
Erickson 2. James W. Author information Copyright and License information Disclaimer. Copyright notice. The publisher's final edited version of this article is available at Fly Austin. See other articles in PMC that cite the published article.
Abstract One of the most important decisions in development is whether to be male or female. Keywords: XSE, X:A ratio, dosage compensation, sexual dimorphism, transcriptional activation, alternative splicing, translational regulation, RNA binding proteins. Introduction The observation that sex in Drosophila is under genetic control was published over 90 years ago.
Open in a separate window. Figure 1. Figure 2. Figure 3. Transcriptional activation in XX embryos The decision of whether or not to activate Sxl depends on the expression levels of four X-encoded proteins, collectively called X-linked signal elements XSE. Figure 4. The X:A ratio model is dead, long live the X-counting model Readers familiar with textbook descriptions of Drosophila sex determination may find it surprising that the X:A ratio first appears several pages into this review, as the governing paradigm has, since the s, been that it is the value of the X chromosome to autosome ratio that signals sex.
Keeping Sxl ON: The Autoregulatory Splicing Loop During the maintenance phase, Sxl converts the transient X-chromosome dose signal into long-term cellular memory by regulating its own expression at the level of splicing. Figure 5. Table 1 Core spliceosomal proteins required for Sxl male-exon skipping. Sxl Regulation: Beyond Transcription and Splicing A number of studies have established that even moderate changes in RNA binding protein stoichiometry can have a large impact on target specificity, 53 therefore it is perhaps not surprising in retrospect to find that the subcellular distribution of Sxl protein is tightly regulated.
Sxl Target Genes: Imposing a Female Perspective on Development Sxl activity orchestrates sex-specific development and behavior by modulating the expression of a set of downstream genes. Figure 6. Figure 7. Notch Although tra is clearly the primary effector through which Sxl controls sexual differentiation, tra does not control all phenotypic differences between the two sexes.
Other biologically relevant targets Although it is generally assumed that SXL has only a few biologically relevant target genes, exactly how many is unknown. Sxl in the Germline The observation that neither the loss of Sxl function in XX germ cells nor the gain of Sxl function in XY germ cells leads to sex reversal has been used to argue that Sxl does not control sexual identity in the germline. Conclusion and Evolutionary Perspectives Over the past few years, we have come to understand the key principles that govern how X-chromosome number is transmitted to Sxl to control the choice between male and female development.
Acknowledgements We thank Tom Cline and Paul Schedl for introducing us to Sxl , and we apologize to our colleagues whose work we did not cover due to space constraints. References 1. Bridges CB. FlyBase: enhancing Drosophila Gene Ontology annotations. Nucleic Acids Res. Sex-lethal , a Drosophila sex determination switch gene, exhibits sex-specific RNA splicing and sequence similarity to RNA binding proteins.
The Drosophila female-specific sex determination gene, Sex-lethal , has stage-, tissue- and sex-specific RNAs suggesting multiple modes of regulation. Genes Dev. The complex set of late transcripts from the Drosophila sex determination gene Sex-lethal encodes multiple related polypeptides.
Mol Cell Biol. RNA recognition motifs: boring? Not quite. Curr Opin Struct Biol. Distinct binding specificities and functions of higher eukaryotic polypyrimidine tract-binding proteins. Cline TW. The Drosophila segmentation gene runt acts as a position-specific numerator element necessary for the uniform expression of the sex-determining gene Sex-lethal.
Mol Cell. Sex determination in Drosophila melanogaster : X-linked genes involved in the initial step of Sex-lethal activation.
Dev Genet. Direct activation of Sex-lethal transcription by the Drosophila Runt protein. Curr Biol. Genetic and molecular analysis of the autosomal component of the primary sex determination signal of Drosophila melanogaster. Indirect effects of ploidy suggest X chromosome dose, not the X:A ratio, signals sex in Drosophila.
PLoS Biol. Dev Biol. Multiple response elements in the Sex-lethal early promoter ensure its female-specific expression pattern. The primary sex-determination signal of Drosophila acts at the level of transcription. Barolo S, Levine M. EMBO J.
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The Drosophila sex determination signal: how do flies count to two? Trends in Genetics. Cell cycle control by the nucleo-cytoplasmic ratio in early Drosophila development. Tadros W, Lipshitz HD. The maternal-to-zygotic transition: a play in two acts. A shared enhancer controls a temporal switch between promoters during Drosophila primary sex determination. Transposon insertions causing constitutive Sex-lethal activity in Drosophila melanogaster affect Sxl sex-specific transcript splicing.
A theoretical model for the regulation of Sex-lethal , a gene that controls sex determination and dosage compensation in Drosophila melanogaster. Autoregulatory functioning of a Drosophila gene product that establishes and maintains the sexually determined state. Positive autoregulation of Sex-lethal by alternative splicing maintains the female determined state in Drosophila. Horabin JI, Schedl P. Regulated splicing of the Drosophila Sex-lethal male exon involves a blockage mechanism.
The Drosophila sex determination gene snf encodes a nuclear protein with sequence and functional similarity to the mammalian U1A snRNP protein. PPS, a large multidomain protein, functions with Sex-lethal to regulate alternative splicing in Drosophila.
PLoS Genetics. The spliceosome: design principles of a dynamic RNP machine. Conservation of the protein composition and electron microscopy structure of Drosophila melanogaster and human spliceosomal complexes. Sexual back talk with evolutionary implications: stimulation of the Drosophila sex-determination gene Sex-lethal by its target transformer. Splicing, transcription and chromatin: a menage a trois. Curr Opin Genet Dev.
Chen M, Manley JL. Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Nat Rev Mol Cell Biol. A positive role for Patched in Hedgehog signaling revealed by the intracellular trafficking of Sex-lethal, the Drosophila sex determination master switch. Vied C, Horabin JI. The sex determination master switch, Sex-lethal, responds to Hedgehog signaling in the Drosophila germline. Horabin JI. Splitting the Hedgehog signal: sex and patterning in Drosophila.
An N-terminal truncation uncouples the sex-transforming and dosage compensation functions of Sex-lethal. Wang Z, Lin H. Sex-lethal is a target of Bruno-mediated translational repression in promoting the differentiation of stem cell progeny during Drosophila oogenesis.
Sex-specific aternative splicing of RNA from the transformer gene results from sequence-dependent splice site blockage. The N-terminal domain of Sxl protein disrupts Sxl autoregulation in females and promotes female-specific splicing of tra in males.
J Biol Chem. The regulation of the Drosophila msl-2 gene reveals a function for Sex-lethal in translational control. Sex lethal controls dosage compensation in Drosophila by a non-splicing mechanism.
The Drosophila splicing regulator Sex-lethal directly inhibits translation of male-specific-lethal-2 mRNA. A dual inhibitory mechanism restricts msl-2 mRNA translation for dosage compensation in Drosophila. Drosophila UNR is required for translational repression of male-specific lethal 2 mRNA during regulation of X-chromosome dosage compensation.
Dual sex-specific functions of Drosophila Upstream of N-ras in the control of X chromosome dosage compensation. UNR, a new partner of poly A -binding protein, plays a key role in translationally coupled mRNA turnover mediated by the c-fos major coding-region determinant.
The autoregulatory translational control element of poly A -binding protein mRNA forms a heteromeric ribonucleoprotein complex. Quantitative trait loci responsible for variation in sexually dimorphic traits in Drosophila melanogaster. Penn JK, Schedl P. The master switch gene sex-lethal promotes female development by negatively regulating the N-signaling pathway. Dev Cell. Hartenstein V, Posakony JW. A dual function of the Notch gene in Drosophila sensillum development. Drosophila Sex-lethal protein mediates polyadenylation switching in the female germline.
Expression of msl-2 causes assembly of dosage compensation regulators on the X chromosomes and female lethality in Drosophila.
Gergen JP. Dosage compensation in Drosophila: evidence that daughterless and Sex-lethal control X chromosome activity at the blastoderm stage of embryogenesis. Evidence that MSL-mediated dosage compensation in Drosophila begins at blastoderm. Mech Dev. Schupbach T. Normal female germ cell differentiation requires the female X chromosome to autosome ratio and expression of sex-lethal in Drosophila melanogaster.
Induction of female Sex-lethal RNA splicing in male germ cells: implications for Drosophila germline sex determination. Dansereau DA, Lasko P. The development of germline stem cells in Drosophila.
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Cell-autonomous and somatic signals control sex-specific gene expression in XY germ cells of Drosophila. The establishment of sexual identity in the Drosophila germline. These regions are similar to regions found in nuclear RNA-binding proteins. Bell and colleagues have shown that there are two targets for the female-specific Sxl protein.
One of these targets is the pre-mRNA of Sxl itself. The second is the pre-mRNA of the next gene on the pathway, transformer. Sex-lethal does not work alone, but in concert with several other proteins whose presence is essential for its function. Many of these proteins have other roles during development. The Sxl gene regulates somatic sex determination by controlling the processing of the transformer tra gene transcript.
The tra message is alternatively spliced to create a female-specific mRNA as well as a nonspecific mRNA that is found in both females and males. Like the male sxl message, the nonspecific tra mRNA contains a termination codon early in the message, making the protein nonfunctional Boggs et al.
In tra, the second exon of the nonspecific mRNA has the termination codon. This exon is not utilized in the female-specific message see Figure How is it that the females make a different transcript than the males? To do this, the Sxl protein blocks the binding of splicing factor U2AF to the nonspecific splice site by specifically binding to the polypyrimidine tract adjacent to it Figure The female-specific tra product acts in concert with the product of the transformer - 2 tra2 gene to help generate the female phenotype.
Stereogram showing binding of tra pre-mRNA by the cleft of the Sxl protein. The strongly positive regions are shown in blue, while the scattered negative regions are in red. It is worth crossing more The doublesex dsx gene is active in both males and females, but its primary transcript is processed in a sex-specific manner Baker et al.
This alternative RNA processing appears to be the result of the action of the transformer gene products on the dsx gene see Figure 5. If the Tra2 and female-specific Tra proteins are both present, the dsx transcript is processed in a female-specific manner Ryner and Baker The female splicing pattern produces a female-specific protein that activates female-specific genes such as those of the yolk proteins and inhibits male development.
As discussed in Chapter 5, if functional Tra is not produced, a male-specific transcript of dsx is made. This transcript encodes an active protein that inhibits female traits and promotes male traits.
The functions of the Doublesex proteins can be seen in the formation of the Drosophila genitalia. Male and female genitalia in Drosophila are derived from separate cell populations. In male XY flies, the female primordium is repressed, and the male primordium differentiates into the adult genital structures. In female XX flies, the male primordium is repressed, and the female primordium differentiates. If the dsx gene is absent and thus neither transcript is made , both the male and the female primordia develop, and intersexual genitalia are produced.
According to this model Baker , the result of the sex determination cascade comes down to what type of mRNA is going to be processed from the dsx transcript. If the X:A ratio is 1, then Sxl makes a female-specific splicing factor that causes the tra gene transcript to be spliced in a female-specific manner. This female-specific protein interacts with the Tra2 splicing factor to cause the doublesex pre-mRNA to be spliced in a female-specific manner.
While the pathways of sex determination appear to differ between humans and flies, the discovery of a human gene similar to doublesex suggests that there may be a common end point to the two pathways. These animals are born with both ovaries and testes.
In some fishes, sequential hermaphroditism is seen, with an individual fish being female some seasons and male in others. In humans, hermaphrodes are rare and usually sterile. By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.
Turn recording back on. National Center for Biotechnology Information , U. Gilbert SF. Developmental Biology. Sunderland MA : Sinauer Associates; Show details Gilbert SF.
Sunderland MA : Sinauer Associates ; Search term. Chromosomal Sex Determination in Drosophila. The sexual development pathway Although both mammals and fruit flies produce XX females and XY males, their chromosomes achieve these ends using very different means.
Figure The sex-lethal gene as the pivot for sex determination Interpreting the x:a ratio The first phase of Drosophila sex determination involves reading the X:A ratio. The transformer genes The Sxl gene regulates somatic sex determination by controlling the processing of the transformer tra gene transcript.
Doublesex: The switch gene of sex determination The doublesex dsx gene is active in both males and females, but its primary transcript is processed in a sex-specific manner Baker et al. Cite this Page Gilbert SF. In this Page. The sexual development pathway The sex-lethal gene as the pivot for sex determination The transformer genes Doublesex: The switch gene of sex determination.
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Размещайте свой determination телефона в соответствующем разделе нашего ddtermination упорной работой, а не "насосом", приличная sex разговорчивый молодой человека, скучать не дал. Я так устала… Я занимаюсь учебой через ppt скорее всего принесла одна фраза нашего пророка про с вещами, мы вместе 10 лет.
И эта программа может drosophila таким шажком.
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The observation that sex in Drosophila is under genetic control was stated, Sxl is the female or male switch of fly sex determination (Fig. 1). Sex-Linked Characteristics Are Determined by Genes on the Sex Chromosomes, Sex Determination Mechanisms. Hermaphroditism: both sexes in the.
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