Males and females: Creating differences while maintaining the similarities

Suissa, Yaron; Ordan, Elly; Deshpande, Girish; Gerlitz, Offer

doi:10.4161/fly.5.1.13995

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…Sxl controls the sex determination and dosage compensation pathways by regulating the expression of transformer and male-specific-lethal-2 genes, but neither of these genes has a role in the germline (17)(18)(19). Notch transcripts are also subject to Sxl regulation, but only in a subset of somatic cells (20)(21)(22). Additional candidate genes have been identified by bioinformatic approaches, but their biological relevance to germline differentiation has yet to be established (23,24).…”

mentioning

confidence: 99%

Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis

Chau

Kulnane

Salz

2012

Proc. Natl. Acad. Sci. U.S.A.

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Drosophila ovarian germ cells require Sex-lethal (Sxl) to exit from the stem cell state and to enter the differentiation pathway. Sxl encodes a female-specific RNA binding protein and in somatic cells serves as the developmental switch gene for somatic sex determination and X-chromosome dosage compensation. None of the known Sxl target genes are required for germline differentiation, leaving open the question of how Sxl promotes the transition from stem cell to committed daughter cell. We address the mechanism by which Sxl regulates this transition through the identification of nanos as one of its target genes. Previous studies have shown that Nanos protein is necessary for GSC self-renewal and is rapidly down-regulated in the daughter cells fated to differentiate in the adult ovary. We find that this dynamic expression pattern is limited to female germ cells and is under Sxl control. In the absence of Sxl, or in male germ cells, Nanos protein is continuously expressed. Furthermore, this female-specific expression pattern is dependent on the presence of canonical Sxl binding sites located in the nanos 3′ untranslated region. These results, combined with the observation that nanos RNA associates with the Sxl protein in ovarian extracts and loss and gain of function studies, suggest that Sxl enables the switch from germline stem cell to committed daughter cell by posttranscriptional down-regulation of nanos expression. These findings connect sexual identity to the stem cell self-renewal/differentiation decision and highlight the importance of posttranscriptional gene regulatory networks in controlling stem cell behavior.

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confidence: 99%

Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis

Chau

Kulnane

Salz

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…It functions as homeotic factor to prevent accumulation of excessive levels of Sxl thus allowing proper N expression and preventing toxicity . It has been proposed that, in order to regulate Sxl expression, Hrp48 requires the Sxl protein itself, such that if Sxl levels become too low, regulation is alleviated . This would provide an additional regulatory mechanism to carefully balance Sxl concentrations and to prevent accumulation of excessive protein levels.…”

Section: Balancing Sxl Expression—finding the Right Concentration Formentioning

confidence: 99%

“…Finally, it appears as if not all regulatory partners of Sxl have yet been identified. YT521‐B and Hrp48 have been proposed to function together with Sxl in gene regulation . Moreover, despite ubiquitous expression of Sxl, regulation of e(r) APA is germline specific and potentially involves additional regulatory factors.…”

Section: Sxl As Versatile Regulator Of Partnerships and Competitionmentioning

confidence: 99%

Promiscuity in post‐transcriptional control of gene expression: Drosophila sex‐lethal and its regulatory partnerships

2017

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The Drosophila RNA‐binding protein Sex‐lethal (Sxl) is a potent post‐transcriptional regulator of gene expression that controls female development. It regulates the expression of key factors involved in sex‐specific differences in morphology, behavior, and dosage compensation. Functional Sxl protein is only expressed in female flies, where it binds to U‐rich RNA motifs present in its target mRNAs to regulate their fate. Sxl is a very versatile regulator that, by shuttling between the nucleus and the cytoplasm, can regulate almost all aspects of post‐transcriptional gene expression including RNA processing, nuclear export, and translation. For these functions, Sxl employs multiple interactions to either antagonize RNA‐processing factors or to recruit various coregulators, thus allowing it to establish a female‐specific gene expression pattern. Here, we summarize the current knowledge about Sxl function and review recent mechanistic and structural studies that further our understanding of how such a seemingly ‘simple’ RNA‐binding protein can exert this plethora of different functions.

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Sex determination in insects: a binary decision based on alternative splicing

Salz

2011

Current Opinion in Genetics & Development

138

117

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The gene regulatory networks that control sex determination vary between species. Despite these differences, comparative studies in insects have found that alternative splicing is reiteratively used in evolution to control expression of the key sex determining genes. Sex determination is best understood in Drosophila where activation of the RNA binding protein encoding gene Sex-lethal is the central female-determining event. Sex-lethal serves as a genetic switch because once activated it controls its own expression by a positive feedback splicing mechanism. Sex fate choice in is also maintained by self-sustaining positive feedback splicing mechanisms in other dipteran and hymenopteran insects, although different RNA binding protein encoding genes function as the binary switch. Studies exploring the mechanisms of sex-specific splicing have revealed the extent to which sex determination is integrated with other developmental regulatory networks.

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Males and females: Creating differences while maintaining the similarities

Cited by 5 publications

References 20 publications

Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis

Sex-lethal enables germline stem cell differentiation by down-regulating Nanos protein levels during Drosophila oogenesis

Promiscuity in post‐transcriptional control of gene expression: Drosophila sex‐lethal and its regulatory partnerships

Sex determination in insects: a binary decision based on alternative splicing

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