Lessons from an unusual vertebrate sex-determining gene Bertho, Sylvain; Herpin, Amaury; Schartl, Manfred ...
Philosophical transactions - Royal Society. Biological sciences,
08/2021, Volume:
376, Issue:
1832
Journal Article
Peer reviewed
Open access
So far, very few sex-determining genes have been identified in vertebrates and most of them, the so-called ‘usual suspects’, evolved from genes which fulfil essential functions during sexual ...development and are thus already tightly linked to the process that they now govern. The single exception to this ‘usual suspects’ rule in vertebrates so far is the conserved salmonid sex-determining gene,
sdY
(sexually dimorphic on the Y chromosome), that evolved from a gene known to be involved in regulation of the immune response. It is contained in a jumping sex locus that has been transposed or translocated into different ancestral autosomes during the evolution of salmonids. This special feature of
sdY
, i.e. being inserted in a ‘jumping sex locus’, could explain how salmonid sex chromosomes remain young and undifferentiated to escape degeneration. Recent knowledge on the mechanism of action of
sdY
demonstrates that it triggers its sex-determining action by deregulating oestrogen synthesis that is a conserved and crucial pathway for ovarian differentiation in vertebrates. This result suggests that
sdY
has evolved to cope with a pre-existing sex differentiation regulatory network. Therefore, ‘limited options’ for the emergence of new master sex-determining genes could be more constrained by their need to tightly interact with a conserved sex differentiation regulatory network rather than by being themselves ‘usual suspects’, already inside this sex regulatory network.
This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)’.
Fertility and gamete reserves are maintained by asymmetric divisions of the germline stem cells to produce new stem cells or daughters that differentiate as gametes. Before entering meiosis, ...differentiating germ cells (GCs) of sexual animals typically undergo cystogenesis. This evolutionarily conserved process involves synchronous and incomplete mitotic divisions of a GC daughter (cystoblast) to generate sister cells connected by intercellular bridges that facilitate the exchange of materials to support rapid expansion of the gamete progenitor population. Here, we investigated cystogenesis in zebrafish and found that early GCs are connected by ring canals, and show that Deleted in azoospermia-like (Dazl), a conserved vertebrate RNA-binding protein (Rbp), is a regulator of this process. Analysis of dazl mutants revealed the essential role of Dazl in regulating incomplete cytokinesis, germline cyst formation and germline stem cell specification before the meiotic transition. Accordingly, dazl mutant GCs form defective ring canals, and ultimately remain as individual cells that fail to differentiate as meiocytes. In addition to promoting cystoblast divisions and meiotic entry, dazl is required for germline stem cell establishment and fertility.
Evolutionary novelties require rewiring of transcriptional networks and/or the evolution of new gene functions. Sex determination (SD), one of the most plastic evolutionary processes, requires such ...novelties. Studies on the evolution of vertebrate SD revealed that new master SD genes are generally recruited from genes involved in the downstream SD regulatory genetic network. Only a single exception to this rule is currently known in vertebrates: the intriguing case of the salmonid master SD gene (sdY), which arose from duplication of an immune-related gene. This exception immediately posed the question of how a gene outside from the classical sex differentiation cascade could acquire its function as a male SD gene. Here we show that SdY became integrated in the classical vertebrate sex differentiation cascade by interacting with the Forkhead box domain of the female-determining transcription factor, Foxl2. In the presence of Foxl2, SdY is translocated to the nucleus where the SdY:Foxl2 complex prevents activation of the aromatase (cyp19a1a) promoter in cooperation with Nr5a1 (Sf1). Hence, by blocking a positive loop of regulation needed for the synthesis of estrogens in the early differentiating gonad, SdY disrupts a preset female differentiation pathway, consequently allowing testicular differentiation to proceed. These results also suggest that the evolution of unusual vertebrate master sex determination genes recruited from outside the classical pathway like sdY is strongly constrained by their ability to interact with the canonical gonadal differentiation pathway.
A novel regio‐ and diastereoselective iron‐catalyzed intermolecular oxyazidation of enamides using various azidobenziodoxolone (ABX) derivatives is presented. A variety of α‐N3 amino derivatives and ...of α‐N3 piperidines were synthesized in good yields and under mild reaction conditions. The reaction involves a radical process using cheap FeCl2 as the initiator.
Iron catalysis: An iron‐catalyzed oxyazidation of enamides was developed. This provided an efficient route to α‐N3 amino derivatives and more specifically α‐N3 piperidine derivatives in good yields with high regio‐ and diastereoselectivity.
Foxl2 is a member of the large family of Forkhead Box (Fox) domain transcription factors. It emerged during the last 15 years as a key player in ovarian differentiation and oogenesis in vertebrates ...and especially mammals. This review focuses on Foxl2 genes in light of recent findings on their evolution, expression, and implication in sex differentiation in animals in general. Homologs of Foxl2 and its paralog Foxl3 are found in all metazoans, but their gene evolution is complex, with multiple gains and losses following successive whole genome duplication events in vertebrates. This review aims to decipher the evolutionary forces that drove Foxl2/3 gene specialization through sub- and neo-functionalization during evolution. Expression data in metazoans suggests that Foxl2/3 progressively acquired a role in both somatic and germ cell gonad differentiation and that a certain degree of sub-functionalization occurred after its duplication in vertebrates. This generated a scenario where Foxl2 is predominantly expressed in ovarian somatic cells and Foxl3 in male germ cells. To support this hypothesis, we provide original results showing that in the pea aphid (insects) foxl2/3 is predominantly expressed in sexual females and showing that in bovine ovaries FOXL2 is specifically expressed in granulosa cells. Overall, current results suggest that Foxl2 and Foxl3 are evolutionarily conserved players involved in somatic and germinal differentiation of gonadal sex.
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