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Wagner, S.

Publications and source records attributed to Wagner, S..

At least 55 records · Page 3Linked to original sources

Simultaneous recording of ultrasonic vocalizations and sniffing from socially interacting individual rats using a miniature microphone

Vocalizations are pivotal in mammalian communication, especially in humans. Rodents accordingly rely on ultrasonic vocalizations (USVs) that reflect their internal state as a primary channel during social interactions. However, attributing vocalizations to specific individuals remains challenging, impeding internal state assessment. Rats emit 50 kHz USVs to indicate positive states and intensify sniffing during alertness and social interactions. Here, we present a method involving a miniature microphone attached to the rat nasal cavity that allows to capture both male and female individual rat vocalizations and sniffing patterns during social interactions. We found that while the emission of 50 kHz USVs increases during close interactions, these signals lack specific behavioral associations. Moreover, a previously unreported low-frequency vocalization type marking rat social interactions was uncovered. Finally, different dynamics of sniffing and vocalization activities point to distinct underlying internal states. Thus, our method facilitates the exploration of internal states concurrent with social behaviors. MotivationHere, we sought to solve the problem of identifying the emitter of a specific vocalization during free social interaction of animal models. The use of a miniature microphone carried by the subject and connected to its nasal cavity solved this challenge and allowed for assignment of any vocalization recorded during a social interaction to a specific individual. Moreover, the miniature microphone enabled simultaneous recording of sniffing and vocalization activities of an individual, thus facilitating recognition of the internal states underlying these traits.

animal behavior and cognition↗

Altered iron-sulfur cluster transfer in Arabidopsis mitochondria reveals lipoyl synthase as a Janus-faced enzyme that generates toxic sulfide

Iron-sulfur (Fe-S) cluster are vital cofactors in all domains of life. Mitochondrial Fe-S cluster assembly occurs in two major steps to first build [2Fe-2S] clusters and subsequently assemble these into [4Fe-4S] clusters. The two assembly machineries are interconnected by glutaredoxin S15 (GRXS15) that transfers [2Fe-2S] clusters to the second machinery. Diminished cluster transfer activity of GRXS15 in Arabidopsis mitochondria causes specific defects associated with lipoyl synthase (LIP1) activity. Conversely, overexpression of LIP1 in wild-type plants causes the release of toxic amounts of sulfide that can be detoxified by increasing the capacity for sulfide fixation through overexpression of O-acetylserine-(thiol)-lyase. The release of sulfide by lipoyl synthase causes a disturbance of mitochondrial sulfide homeostasis resulting in distinct and readily observable macroscopic phenotypes. These phenotypes enable a direct readout of consequences resulting from defects in Fe-S cluster assembly or targeted modulation of Fe-S cluster flux in mitochondria.

plant biology↗

eIF3e and eIF3d control expression of riboproteins and key components of the MAPK signaling pathway.

Protein synthesis plays a major role in homeostasis and when dysregulated leads to various pathologies including cancer. To this end, imbalanced expression of eukaryotic translation initiation factors (eIFs) is not only a consequence but also a driver of neoplastic growth. eIF3 is the largest, multi-subunit translation initiation complex with a modular assembly, where aberrant expression of one subunit generates only partially functional subcomplexes. To comprehensively study the effects of eIF3 remodeling, we contrasted the impact of eIF3d, eIF3e or eIF3h depletion on the translatome of HeLa cells using Ribo-seq. Depletion of eIF3d or eIF3e, but not eIF3h reduced the levels of multiple components of the MAPK signaling pathways. Surprisingly, however, depletion of all three eIF3 subunits increased MAPK/ERK pathway activity. Depletion of eIF3e and partially eIF3d also increased translation of TOP mRNAs that encode mainly ribosomal proteins and other components of the translational machinery. Moreover, alterations in eIF3 subunit stoichiometry were often associated with changes in translation of mRNAs containing short uORFs, as in the case of the proto-oncogene MDM2 and the transcription factor ATF4. Collectively, perturbations in eIF3 subunit stoichiometry exert specific effect on the translatome comprising signaling and stress-related transcripts with complex 5 UTRs that are implicated in homeostatic adaptation to stress and cancer.

molecular biology↗

Ventral dentate gyrus-dominated LFP rhythmicity in the social brain reflects the context of social encounters

Mammalian social behavior is highly context-sensitive. Yet, little is known about the mechanisms that modulate social behavior according to its context. Recent studies have revealed a network of mostly limbic brain regions, here termed the "social brain", which regulates social behavior. We hypothesized that coherent theta and gamma rhythms reflect the organization of the social brain regions into functional networks in a context-dependent manner. To test this concept, we simultaneously recorded extracellular activity from multiple social brain regions in mice performing three social discrimination tasks. Local field potential (LFP) rhythmicity across all tasks was dominated by a general internal state. However, during stimulus investigation LFP rhythmicity was sensitive to stimulus characteristics. Specifically, the pattern of LFP coherence between the various regions reflected mainly the social context. Moreover, we found the ventral dentate gyrus to play a pivotal role in coordinating the context-specific rhythmic activity in the network.

neuroscience↗

HilE represses the activity of HilD via a mechanism distinct from that of intestinal long-chain fatty acids.

The expression of virulence factors essential for the invasion of host cells by Salmonella enterica is tightly controlled by a network of transcription regulators. The AraC/XylS transcription factor HilD is the main integration point of environmental signals into this regulatory network, with many factors affecting HilD activity. Long chain fatty acids (LCFAs), which are highly abundant throughout the host intestine directly bind to, and repress HilD, acting as environmental cues to coordinate virulence gene expression. The regulatory protein HilE also negatively regulates HilD activity, through a protein-protein interaction. Both of these regulators inhibit HilD dimerisation, preventing HilD from binding to target DNA. We investigated the structural basis of these mechanisms of HilD repression. LCFAs bind to a conserved pocket in HilD, in a comparable manner to that reported for other AraC/XylS regulators, whereas HilE forms a stable heterodimer with HilD by binding to the HilD dimerisation interface. Our results highlight two distinct mechanisms by which HilD activity is repressed, which could be exploited for the development of new antivirulence leads.

biochemistry↗

Basolateral amygdala circuits supporting negative emotional bias in a mouse model for depression

Negative emotional bias is an essential hallmark of depression reflected by negative shift in hedonic valence assignment to emotional stimuli. Pleasant cues become less attractive and unpleasant ones more aversive. Given the crucial role of amygdala in valence coding, we hypothesize that specific basolateral amygdala (BLA) circuits alterations might support negative emotional bias associated with depressive states. Using a translational assay, we evaluate odor valence assignment in an animal model for depression chronically administered by corticosterone (CORT). We show spontaneous negative bias in depressive-like mice that attribute more negative valences for both attractive and aversive odors, mimicking thus the bias observed in depressed bipolar patients. Combining CTB and rabies-based tracing with ex vivo measurements of neuronal activity and chemogenetics experiments, we find that the CORT treatment reduces BLA-to-nucleus accumbens (NAc) neuronal activity and increases BLA-to-central amygdala activity, circuits respectively known to be involved in positive and negative valence encoding. Alterations in presynaptic connectivity of BLA-projecting neurons accompany these activity shifts. Interestingly, inputs from the paraventricular thalamus nucleus (PVT) towards BLA-to-NAc neurons are reduced in CORT-treated mice. Finally, chemogenetically activating the BLA-to-NAc circuit attenuates the negative bias in CORT-treated mice as well as the depressive-like phenotype, similarly than Fluoxetine antidepressant treatment. Altogether, we demonstrate that depressive states are associated with negative emotional bias both in human and mice. This bias is supported by activity shifts of specific BLA circuits along with durable presynaptic connectivity changes, but it could be alleviated by antidepressant drug or activity manipulation of altered BLA circuit.

neuroscience↗

Single-cell RNA sequencing analyses of primary cutaneous B-cell disorders reveal distinct molecular patterns consistent with clinical behavior

Primary cutaneous B-cell lymphomas comprise a heterogeneous group of extranodal non-Hodgkin lymphomas. While primary cutaneous diffuse large B-cell lymphoma leg type (pcDLBCL-LT) is highly aggressive, the two other subtypes, primary cutaneous follicle centre lymphoma (pcFCL) and primary cutaneous marginal zone lymphoma (pcMZL), usually follow an indolent course. To better understand the molecular landscape of these entities, we performed single-cell RNA sequencing of pcFCL, pcMZL, and pcDLBCL-LT skin lesions and compared them to B-cell rich lymphoid proliferation (rB-LP) lesions, gastric MALT lymphoma, nodal FCL, and nodal DLBCL. Our data show that these lymphomas can be clearly distinguished from each other on a transcriptomic level based on scRNA-seq. pcMZL, pcFCL, and rB-LP all exhibited a persistent germinal centre reaction as evidenced by the presence of required support cells and continuous somatic hypermutation within the expanded clone. By contrast, malignant clones of pcDLBCL-LT and gastric MALT lymphoma lesions lacked these features. Further, pcMZL top expanded clones were developing within lesions from naive and not post-germinal centre B cells as currently presumed. Therefore, pcMZL may represent a non-malignant reaction against a yet to be determined antigen. Conversely, in pcFCL, B cells showed a larger amount of clonal expansion. The lack of further differentiation of these B cells may explain its indolent clinical course. In contrast to pcDLCBL-LT, our data thus indicate that pcMZL and pcFCL, similar to rB-LP are characterised by a functional germinal centre reaction likely driven by (a yet unknown) antigen recognition, which supports the classification of pcMZL as a lymphoproliferative disease. Key pointsO_LIIndolent B cell neoplasms are uniquely characterised by ongoing, antigen-driven germinal centre reactions. C_LIO_LIPrimary cutaneous B cell lymphomas are distinct entities compared to their systemic counterparts. C_LI

cancer biology↗

Cell types in the mouse amygdala and their transcriptional response to fear conditioning

The amygdala is one of the most widely studied regions in behavioral neuroscience. A plethora of classical, and new paradigms have dissected its precise involvement in emotional and social sensing, learning, and memory. Several important insights resulted from the use of genetic markers - yet, in the age of single cell transcriptomics, the amygdala remains molecularly underdescribed. Here, we present a molecular cell type taxonomy of the full mouse amygdala in fear learning and consolidation. We performed single-cell RNA-seq on naive and fear conditioned mice, inferred the 130 neuronal cell types distributions in silico using orthogonal spatial transcriptomic datasets, and describe the cell types transcriptional responses to learning and memory consolidation. Only a fraction of cells, within a subset of all neuronal types, were transcriptionally responsive to fear learning, memory and retrieval. These activated engram cells upregulated activity-response genes, and processes of synaptic signaling, plasticity, development and neurite outgrowth. Our transcriptome-wide data confirm known actors, and describe several new candidate genes. The atlas may help pinpoint the amygdalas circuits in performing emotional sensing and integration, and provide new insights to the global cellular processes involved.

neuroscience↗

Neural activity and theta rhythmicity in the anterior hypothalamic nucleus are involved in regulating social investigation

Social interactions are highly complex, involving both approach and avoidance actions towards specific individuals, dependent on the social context. Currently, the brain regions subserving these behaviors are not fully known. The anterior hypothalamic nucleus (AHN) is a relatively unstudied and poorly defined brain area, known as part of the medial hypothalamic defensive system. Recent studies that examined the role of the AHN in various contexts have yielded contradicting results regarding its contribution to approach, avoidance, and escape behaviors. Yet, none of these studies has directly examined its role in social interactions. Here we explored the role of AHN neurons in regulating approach and avoidance actions towards distinct stimuli during various types of social interactions, using electrophysiological recording of neural activity in the AHN of behaving mice, c-Fos staining, and direct optogenetic stimulation. We found that theta rhythmicity in the AHN was enhanced during affiliative interactions, but decreased during aversive ones. Moreover, spiking activity of AHN neurons was found to be elevated more persistently during investigation of social stimuli, as compared to objects. Notably, AHN neuronal firing was found to be modulated by theta rhythmicity during social interactions. Finally, we found that during social interaction, direct optogenetic stimulation of AHN neurons augmented approach behavior towards stimuli associated with the optogenetic activation. Overall, our results suggest a context-dependent role for AHN neuronal activity in regulating approach behavior during social interactions, and for theta rhythmicity in mediating the valence of the social context.

neuroscience↗

Dissecting the invasion of Galleria mellonella by Yersinia enterocolitica reveals metabolic adaptations and a role of a phage lysis cassette in insect killing

The human pathogen Yersinia enterocolitica strain W22703 is characterized by its toxicity towards invertebrates that requires the insecticidal toxin complex (Tc) proteins encoded by the pathogenicity island Tc-PAIYe. Molecular and pathophysiological details of insect larvae infection and killing by this pathogen, however, have not been dissected. Here, we applied oral infection of Galleria mellonella (Greater wax moth) larvae to study the colonisation, proliferation, tissue invasion, and killing activity of W22703. We demonstrated that this strain is strongly toxic towards the larvae, in which they proliferate by more than three orders of magnitude within six days post infection. Deletion mutants of genes tcaA and tccC were atoxic for the insect. W22703 {Delta}tccC, in contrast to W22703 {Delta}tcaA, initially proliferated before being eliminated from the host, thus confirming TcaA and TccC as membrane-binding Tc subunit and ADP-ribosylating enzyme, respectively. Time course experiments revealed a Tc-dependent infection process starting with midgut colonisation that is followed by invasion of the hemolymph where the pathogen elicits morphological changes of hemocytes and strongly proliferates. The in vivo transcriptome of strain W22703 shows that the pathogen undergoes a drastic reprogramming of central cell functions and gains access to numerous carbohydrate and amino acid resources within the insect. Strikingly, a mutant lacking a phage-related holin/endolysin (HE) cassette, which is located within Tc-PAIYe, resembled the phenotypes of W22703 {Delta}tcaA, suggesting that this dual lysis cassette is an example for a phage-related function that has been adapted for the release of a bacterial toxin.

microbiology↗

Oxytocin activity in the Paraventricular and Supramammillary Nuclei of the Hypothalamus is Essential for Social Recognition Memory in Rats

Oxytocin plays an important role in modulating social recognition memory. However, the direct implication of oxytocin neurons of the paraventricular nucleus of the hypothalamus (PVH) and their downstream hypothalamic targets in regulating short- and long-term forms of social recognition memory has not been fully investigated. In this study, we employed a chemogenetic approach to target the activity of PVH oxytocin neurons in male rats and found that specific silencing of this neuronal population led to an impairment in short- and long-term social recognition memory. We combined viral mediated fluorescent labeling of oxytocin neurons with immunohistochemical techniques and identified the supramammillary nucleus (SuM) of the hypothalamus as a target of PVH oxytocinergic axonal projections in rats. We used multiplex fluorescence in-situ hybridization to label oxytocin receptors in the SuM and determined that they are predominantly expressed in glutamatergic neurons, including those that project to the CA2 region of the hippocampus. Finally, we used a highly selective oxytocin receptor antagonist in the SuM to examine the involvement of oxytocin signaling in modulating short- and long-term social recognition memory and found that it is necessary for the formation of both. This study discovered a previously undescribed role for the SuM in regulating social recognition memory via oxytocin signaling and reinforced the specific role of PVH oxytocin neurons in regulating this form of memory.

neuroscience↗

Obesity medication lorcaserin requires brainstem GLP-1 neurons to reduce food intake in mice

Overweight and obesity are rapidly becoming the "new normal" in developed countries, which promotes a widespread negative impact on human health. Amongst recently developed obesity medications are the serotonin 2C receptor (5-HT2CR) agonist lorcaserin and glucagon-like peptide-1 receptor (GLP-1R) agonists, but the brain circuits employed by these medications to produce their therapeutic effects remain to be fully defined. 5-HT2CRs and GLP-1Rs are widely distributed in the brain, including in the key homeostatic region the nucleus of the solitary tract (NTS) where GLP-1 is produced by preproglucagon (PPGNTS) neurons. PPGNTS cells were profiled using histochemistry and single nucleus RNA sequencing (Nuc-Seq) of mouse brainstem. Transcriptomic analyses revealed 5-HT2CR expression was widespread in PPGNTS clusters. Demonstrating the functional significance of this co-expression, lorcaserin required PPGNTS to reduce food intake. Analysis of second order neurons revealed that local GLP1-R neurons within the NTS are necessary for 5-HT2CRNTS food intake suppression. In contrast, GLP-1RNTS were not required for GLP-1R agonist liraglutide and exendin-4s short term feeding reduction, suggesting scope for lorcaserin and GLP1-R agonist combination therapy. In support of this, lorcaserin+liraglutide and lorcaserin+exendin-4 produced greater reductions in food intake when administered in combination as compared to monotherapies. These data provide insight into the therapeutic mechanisms of lorcaserin and identify a combination strategy to improve the therapeutic profile of lorcaserin and GLP1-R agonists.

neuroscience↗

Bartonella taylorii: A model organism for studying Bartonella infection in vitro and in vivo

Bartonella spp. are Gram-negative facultative intracellular pathogens that infect diverse mammals and cause a long-lasting intra-erythrocytic bacteremia in their natural host. These bacteria translocate Bartonella effector proteins (Beps) into host cells via their VirB/VirD4 type 4 secretion system (T4SS) in order to subvert host cellular functions, thereby leading to the downregulation of innate immune responses. Most studies on the functional analysis of the VirB/VirD4 T4SS and the Beps were performed with the major zoonotic pathogen Bartonella henselae for which efficient in vitro infection protocols have been established. However, its natural host, the cat, is unsuitable as an experimental infection model. In vivo studies were mostly confined to rodent models using rodent-specific Bartonella species, while the in vitro infection protocols devised for B. henselae are not transferable for those pathogens. The disparities of in vitro and in vivo studies in different species has hampered progress in our understanding of Bartonella pathogenesis. Here we describe the murine-specific strain B. taylorii IBS296 as a new model organism facilitating the study of bacterial pathogenesis both in vitro in cell cultures and in vivo in laboratory mice. We implemented the split NanoLuc luciferase-based translocation assay to study BepD translocation through the VirB/VirD4 T4SS. We found increased effector-translocation into host cells if the bacteria were grown on tryptic soy agar (TSA) plates and experienced a temperature shift immediately before infection. The improved infectivity in vitro could be correlated to an upregulation of the VirB/VirD4 T4SS. Using our adapted infection protocols, we showed BepD-dependent immunomodulatory phenotypes in vitro. In mice, the implemented growth conditions enabled infection by a massively reduced inoculum without having an impact on the course of the intra-erythrocytic bacteremia. The established model opens new avenues to study the role of the VirB/VirD4 T4SS and the translocated Bep effectors in vitro and in vivo.

microbiology↗

Sex-dependent parameters of social behavior show marked variations between distinct laboratory mouse strains and their mixed offspring

BackgroundThe survival of individuals of gregarious species depends on their ability to properly form social interactions. In humans, atypical social behavior is a hallmark of several psychopathological conditions, such as depression and autism spectrum disorder, many of which have sex-specific manifestations. Various strains of laboratory mice are used to reveal the mechanisms mediating typical and atypical social behavior in mammals. MethodsHere we used three social discrimination tests (social preference, social novelty preference, and sex preference) to characterize social behavior in males and females of three widely used laboratory mouse strains (C57BL/6J, BALB/c, and ICR). ResultsWe found marked sex- and strain-specific differences in the preference exhibited by subjects in a test-dependent manner. Interestingly, we found some characteristics that were strain-dependent, while others were sex-dependent. Moreover, even in the social preference test, where both sexes of all strains prefer social over object stimuli, we revealed sex- and strain-specific differences in the behavioral dynamics. We then cross-bred C57BL/6J and BALB/c mice and demonstrated that the offspring of such cross-breeding exhibit a profile of social behavior which is different from both parental strains and depends on the specific combination of parental strains. ConclusionsWe conclude that social behavior of laboratory mice is highly sex- and strain-specific and strongly depends on genetic factors.

animal behavior and cognition↗

Clonal reconstruction from co-occurrence of vector integration sites allows accurate quantification of expanding clones in vivo

High transduction rates of viral vectors in gene therapies (GT) and experimental hematopoiesis ensure a high frequency of gene delivery, although multiple integration events can occur in the same cell. Therefore, tracing of integration sites (IS) leads to misquantification of the true clonal spectrum and limits safety considerations in GT. Hence, we use correlations between repeated measurements of IS abundances to estimate their mutual similarity and identify clusters of co-occurring IS, for which we assume a clonal origin. We evaluate the performance, robustness and specificity of our methodology using clonal simulations. The reconstruction methods, implemented and provided as an R-package, are further applied to experimental clonal mixes and to a preclinical model of hematopoietic GT. Our results demonstrate that clonal reconstruction from IS data allows to overcome systematic biases in the clonal quantification as an essential prerequisite for the assessment of safety and long-term efficacy of GT involving integrative vectors.

cancer biology↗

Uncovering the Bromodomain Interactome using Site-Specific Azide-Acetyllysine Photochemistry, Proteomic Profiling and Structural Characterization

Protein-protein interactions mediated by acetyllysines and bromodomains are essential for the regulation of eukaryotic gene expression. Diagramming the bromodomain interactome network and molecular characterization of these interactions are key to unraveling context-dependent signaling pathways. Herein, we employ a chemoproteomic platform, called interaction-based protein profiling (IBPP), to map the acetylome of the bromodomain and extra terminal domain (BET) family of bromodomains. We developed photo-responsive bromodomain analogues to carry out UV light-induced azide-acetyllysine crosslinking within the recognition cavity of the domain to capture transient interacting partners present in human cells. Subsequent proteomic and biochemical analyses lead to the identification of an array of acetylated interacting factors, which extend the potential function of BET family proteins beyond transcription. We present here eight high-resolution crystal structures of interactome-bound bromodomains that underscore the atypical binding modes and sequence motifs by which BET members recognize an expanded repertoire of acetylated proteins. In addition, we report an acetyllysine-dependent interaction between BRD4 and interleukin enhancer binding factor 3 (ILF3) in human cells, and uncover its role in recruiting transcriptional regulators to the promoter of the Survivin gene, an anti-apoptotic factor overexpressed in a wide range of human neoplasia. Collectively, our work provides a blueprint for engineering bromodomains, establishes IBPP as a robust chemoproteomic tool to characterize bromodomain interactome, and reveals distinctive recognition modes by which such associations may take place in order to modulate signaling pathways. Furthermore, these structural snapshots offer clues to design specific small-molecule inhibitors against the novel BET interactions and paves the path for exploring the biological significance of this newly identified signaling network.

biochemistry↗

MBNL1 and RBFOX1 co-regulate alternative splicing events transcriptome-wide through a conserved buffering mechanism

Alternative splicing (AS) is controlled by cis-regulatory elements recognized by networks of trans-acting factors. Here we investigate modes and mechanisms of AS co-regulation by MBNL1 and RBFOX1, two RNA binding proteins (RBPs) critical for developmental AS transitions. We generated two cell models that express each RBP under separate inducible promoters. Transcriptome-wide categorization of the impacts of RBFOX1 expression on MBNL1 splicing revealed a common co-regulatory mode through which RBFOX1 buffers MBNL1 dose-dependent splicing regulation by reducing the total range of exon inclusion or exclusion. Minigene mutational analysis and in vitro binding experiments suggest that this buffering mechanism occurs through a shared cis-regulatory element previously unidentified as critical for MBNL1-dependent activity. Overall, our studies define a conserved co-regulatory mechanism through which RBFOX1 and MBNL1 can fine-tune and provide redundancy for AS outcomes. These studies indicate overlapping use of RNA motifs with potential implications for when activity of RBPs is disrupted.

biochemistry↗

Two transcriptionally distinct pathways drive female development in a reptile with both genetic and temperature dependent sex determination

How temperature determines sex remains unknown. A recent hypothesis proposes that conserved cellular mechanisms (calcium and redox; CaRe status) sense temperature and identify genes and regulatory pathways likely to be involved in driving sexual development. We take advantage of the unique sex determining system of the model organism, Pogona vitticeps, to assess predictions of this hypothesis. P. vitticeps has ZZ male: ZW female sex chromosomes whose influence can be overridden in genetic males by high temperatures, causing male-to-female sex reversal. We compare a developmental transcriptome series of ZWf females and temperature sex reversed ZZf females. We demonstrate that early developmental cascades differ dramatically between genetically driven and thermally driven females, later converging to produce a common outcome (ovaries). We show that genes proposed as regulators of thermosensitive sex determination play a role in temperature sex reversal. Our study greatly advances the search for the mechanisms by which temperature determines sex. Author SummaryIn many reptiles and fish, environment can determine, or influence, the sex of developing embryos. How this happens at a molecular level that has eluded resolution for half a century of intensive research. We studied the bearded dragon, a lizard that has sex chromosomes (ZZ male and ZW female), but in which that temperature can override ZZ sex chromosomes to cause male to female sex reversal. This provides an unparalleled opportunity to disentangle, in the same species, the biochemical pathways required to make a female by these two different routes. We sequenced the transcriptomes of gonads from developing ZZ reversed and normal ZW dragon embryos and discovered that different sets of genes are active in ovary development driven by genotype or temperature. Females whose sex was initiated by temperature showed a transcriptional profile consistent with the recently-proposed Calcium-Redox hypotheses of cellular temperature sensing. These findings are an important for understanding how the environment influences the development of sex, and more generally how the environment can epigenetically modify the action of genes.

genetics↗