scholarly journals Timing mechanism of sexually dimorphic nervous system differentiation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Laura Pereira ◽  
Florian Aeschimann ◽  
Chen Wang ◽  
Hannah Lawson ◽  
Esther Serrano-Saiz ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Sex Chromosome ◽  
Sexually Dimorphic ◽  
Neuron Type ◽  
Chromosome Configuration ◽  
Opposite Sex ◽  
Male Specific ◽  
Spatial Specificity

The molecular mechanisms that control the timing of sexual differentiation in the brain are poorly understood. We found that the timing of sexually dimorphic differentiation of postmitotic, sex-shared neurons in the nervous system of the Caenorhabditis elegans male is controlled by the temporally regulated miRNA let-7 and its target lin-41, a translational regulator. lin-41 acts through lin-29a, an isoform of a conserved Zn finger transcription factor, expressed in a subset of sex-shared neurons only in the male. Ectopic lin-29a is sufficient to impose male-specific features at earlier stages of development and in the opposite sex. The temporal, sexual and spatial specificity of lin-29a expression is controlled intersectionally through the lin-28/let-7/lin-41 heterochronic pathway, sex chromosome configuration and neuron-type-specific terminal selector transcription factors. Two Doublesex-like transcription factors represent additional sex- and neuron-type specific targets of LIN-41 and are regulated in a similar intersectional manner.

scholarly journals Timing mechanism of sexually dimorphic nervous system differentiation

2018 ◽  
Author(s):  
Laura Pereira ◽  
Florian Aeschimann ◽  
Chen Wang ◽  
Hannah Lawson ◽  
Esther Serrano-Saiz ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factors ◽  
Sexual Maturation ◽  
Sexual Differentiation ◽  
Rna Binding ◽  
Receptor Expression ◽  
Sexually Dimorphic ◽  
Neuron Type ◽  
C Elegans ◽  
Male Specific

ABSTRACTIn all animals, sexual differentiation of somatic tissue is precisely timed, yet the molecular mechanisms that control the timing of sexual differentiation, particularly in the brain, are poorly understood. We have used sexually dimorphic molecular, anatomical and behavioral features of the C. elegans nervous system to decipher a regulatory pathway that controls the precise timing of sexual differentiation. We find that the sexually dimorphic differentiation of postmitotic neurons in the male nervous system is abrogated in animals that carry a mutation in the miRNA let-7 and prematurely executed in animals either lacking the let-7 inhibitor lin-28, or the direct let-7 target lin-41, an RNA-binding, posttranscriptional regulator. We show that an isoform of a phylogenetically conserved transcription factor, lin-29a, is a critical target of LIN-41 in controlling sexual maturation of sex-shared neurons. lin-29a is expressed in a male-specific manner in a subset of sex-shared neurons at the onset of sexual maturation. lin-29a acts cell-autonomously in these neurons to control the expression of sexually dimorphic neurotransmitter switches, sensory receptor expression, neurite anatomy and connectivity, and locomotor behavior. lin-29a is not only required but also sufficient to impose male-specific features at earlier stages of development and in the opposite sex. The temporal, sexual and spatial specificity of lin-29a expression is controlled intersectionally through the lin-28/let-7/lin-41 heterochronic pathway, sex chromosome configuration and neuron type-specific terminal selector transcription factors. Two Doublesex-like transcription factors represent additional neuron-type specific targets of LIN-41 and are regulated in a similar intersectional manner, indicating the existence of modular outputs downstream of the heterochronic pathway. In conclusion, we have provided insights into the molecular logic of the timing of sexual differentiation in the C. elegans nervous system. Remarkably, the lin28/let7 axis also controls the timing of sexual differentiation in mice and humans thereby hinting toward a striking universality of the control mechanisms of sexual differentiation.

scholarly journals SUMO Represses Transcriptional Activity of the Drosophila SoxNeuro and Human Sox3 Central Nervous System–specific Transcription Factors

2005 ◽  
Vol 16 (6) ◽  
pp. 2660-2669 ◽  
Author(s):  
Jean Savare ◽  
Nathalie Bonneaud ◽  
Franck Girard
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Acceptor Site ◽  
Hmg Box ◽  
Sumo Modification

Sry high mobility group (HMG) box (Sox) transcription factors are involved in the development of central nervous system (CNS) in all metazoans. Little is known on the molecular mechanisms that regulate their transcriptional activity. Covalent posttranslational modification by small ubiquitin-like modifier (SUMO) regulates several nuclear events, including the transcriptional activity of transcription factors. Here, we demonstrate that SoxNeuro, an HMG box-containing transcription factor involved in neuroblast formation in Drosophila, is a substrate for SUMO modification. SUMOylation assays in HeLa cells and Drosophila S2 cells reveal that lysine 439 is the major SUMO acceptor site. The sequence in SoxNeuro targeted for SUMOylation, IKSE, is part of a small inhibitory domain, able to repress in cis the activity of two adjacent transcriptional activation domains. Our data show that SUMO modification represses SoxNeuro transcriptional activity in transfected cells. Overexpression in Drosophila embryos of a SoxN form that cannot be targeted for SUMOylation strongly impairs the development of the CNS, suggesting that SUMO modification of SoxN is crucial for regulating its activity in vivo. Finally, we present evidence that SUMO modification of group B1 Sox factors was conserved during evolution, because Sox3, the human counterpart of SoxN, is also negatively regulated through SUMO modification.

scholarly journals Direct glia-to-neuron transdifferentiation gives rise to a pair of male-specific neurons that ensure nimble male mating

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Laura Molina-García ◽  
Carla Lloret-Fernández ◽  
Steven J Cook ◽  
Byunghyuk Kim ◽  
Rachel C Bonnington ◽  
...  
Keyword(s):  
Cell Fate ◽  
Molecular Mechanisms ◽  
Male Mating ◽  
Sexually Dimorphic ◽  
Innate Behaviour ◽  
One Step ◽  
Males And Females ◽  
Direct Transdifferentiation ◽  
Male Specific ◽  
Mating Sequence

Sexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism by which male-specific neurons are generated in Caenorhabditis elegans through the direct transdifferentiation of sex-shared glial cells. This glia-to-neuron cell fate switch occurs during male sexual maturation under the cell-autonomous control of the sex-determination pathway. We show that the neurons generated are cholinergic, peptidergic, and ciliated putative proprioceptors which integrate into male-specific circuits for copulation. These neurons ensure coordinated backward movement along the mate’s body during mating. One step of the mating sequence regulated by these neurons is an alternative readjustment movement performed when intromission becomes difficult to achieve. Our findings reveal programmed transdifferentiation as a developmental mechanism underlying flexibility in innate behaviour.

scholarly journals In silico analysis of the transcriptional regulatory logic of neuronal identity specification throughout the C. elegans nervous system

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Lori Glenwinkel ◽  
Seth R Taylor ◽  
Kasper Langebeck-Jensen ◽  
Laura Pereira ◽  
Molly B Reilly ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factors ◽  
Single Cell ◽  
Expression Profiles ◽  
Neuronal Cell ◽  
In Silico Analysis ◽  
Specific Gene ◽  
Neuron Type ◽  
C Elegans ◽  
Neuronal Identity

The generation of the enormous diversity of neuronal cell types in a differentiating nervous system entails the activation of neuron type-specific gene batteries. To examine the regulatory logic that controls the expression of neuron type-specific gene batteries, we interrogate single cell expression profiles of all 118 neuron classes of the Caenorhabditis elegans nervous system for the presence of DNA binding motifs of 136 neuronally expressed C. elegans transcription factors. Using a phylogenetic footprinting pipeline, we identify cis-regulatory motif enrichments among neuron class-specific gene batteries and we identify cognate transcription factors for 117 of the 118 neuron classes. In addition to predicting novel regulators of neuronal identities, our nervous system-wide analysis at single cell resolution supports the hypothesis that many transcription factors directly co-regulate the cohort of effector genes that define a neuron type, thereby corroborating the concept of so-called terminal selectors of neuronal identity. Our analysis provides a blueprint for how individual components of an entire nervous system are genetically specified.

Transcription factors Mash-1 and Prox-1 delineate early steps in differentiation of neural stem cells in the developing central nervous system

Development ◽  
1999 ◽  
Vol 126 (3) ◽  
pp. 443-456 ◽  
Author(s):  
M.a. Torii ◽  
F. Matsuzaki ◽  
N. Osumi ◽  
K. Kaibuchi ◽  
S. Nakamura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factors ◽  
Cell Differentiation ◽  
Early Development ◽  
Molecular Mechanisms ◽  
Initial Step

Like other tissues and organs in vertebrates, multipotential stem cells serve as the origin of diverse cell types during genesis of the mammalian central nervous system (CNS). During early development, stem cells self-renew and increase their total cell numbers without overt differentiation. At later stages, the cells withdraw from this self-renewal mode, and are fated to differentiate into neurons and glia in a spatially and temporally regulated manner. However, the molecular mechanisms underlying this important step in cell differentiation remain poorly understood. In this study, we present evidence that the expression and function of the neural-specific transcription factors Mash-1 and Prox-1 are involved in this process. In vivo, Mash-1- and Prox-1-expressing cells were defined as a transient proliferating population that was molecularly distinct from self-renewing stem cells. By taking advantage of in vitro culture systems, we showed that induction of Mash-1 and Prox-1 coincided with an initial step of differentiation of stem cells. Furthermore, forced expression of Mash-1 led to the down-regulation of nestin, a marker for undifferentiated neuroepithelial cells, and up-regulation of Prox-1, suggesting that Mash-1 positively regulates cell differentiation. In support of these observations in vitro, we found specific defects in cellular differentiation and loss of expression of Prox-1 in the developing brain of Mash-1 mutant mice in vivo. Thus, we propose that induction of Mash-1 and Prox-1 is one of the critical molecular events that control early development of the CNS.

scholarly journals Sexually dimorphic traits and male-specific differentiation are actively regulated by Doublesex during specific developmental windows in Nasonia vitripennis

2020 ◽  
Author(s):  
Yidong Wang ◽  
Anna Rensink ◽  
Ute Fricke ◽  
Megan C. Riddle ◽  
Carol Trent ◽  
...  
Keyword(s):  
Male Genitalia ◽  
Molecular Mechanisms ◽  
Parasitoid Wasp ◽  
Tissue Growth ◽  
Parasitoid Wasps ◽  
Sexually Dimorphic ◽  
Nasonia Vitripennis ◽  
Biological Pest Control ◽  
Male Specific ◽  
Developmental Windows

AbstractSexually dimorphic traits in insects are rapidly evolving due to sexual selection which can ultimately lead to speciation. However, our knowledge of the underlying sex-specific molecular mechanisms is still scarce. Here we show that the highly conserved gene, Doublesex (Dsx), regulates rapidly diverging sexually dimorphic traits in the model parasitoid wasp Nasonia vitripennis (Hymenoptera: Pteromalidae). We present here the revised full Dsx gene structure with an alternative first exon, and two additional male NvDsx isoforms, which gives important insights into the evolution of the sex-specific oligomerization domains and C-termini. We show the sex-specific NvDsx expression throughout development, and demonstrate that transient NvDsx silencing in different male developmental stages dramatically shifts the morphology of two sexually dimorphic traits from male to female, with the effect being dependent on the timing of silencing. In addition, transient silencing of NvDsx in early male larvae affects male genitalia tissue growth but not morphology. This indicates that male NvDsx is actively required to suppress female-specific traits and to promote male-specific traits during specific developmental windows. These results also strongly suggest that in N. vitripennis most sex-specific tissues fully differentiate in the embryonic stage and only need the input of NvDsx for growth afterwards. This provides a first insight into the regulatory activity of Dsx in the Hymenoptera and will help to better understand the evolutionary and molecular mechanisms involved in sex-specific development in this parasitoid wasp, which can eventually lead to the development of new synthetic genetics-based tools for biological pest control by parasitoid wasps.Significance StatementIn insects, male and female differentiation is regulated by the highly conserved transcription factor Doublesex (Dsx). The role of Dsx in regulating rapidly evolving sexually dimorphic traits has received less attention, especially in wasps and bees. Here, we mainly focused on Dsx regulation of two sexually dimorphic traits and male genitalia morphology in the parasitoid wasp, Nasonia vitripennis. We demonstrate that Dsx actively regulates male-specific tissue growth and morphology during specific developmental windows. These findings will help to better understand the molecular mechanisms underlying the rapid evolution of sexual differentiation and sexually dimorphic traits in insects, but may also be the starting point for the development of new tools for biological control of pest insects by parasitoid wasps.

scholarly journals Male-Specific Fruitless Isoforms Target Neurodevelopmental Genes to Specify a Sexually Dimorphic Nervous System

2014 ◽  
Vol 24 (3) ◽  
pp. 229-241 ◽  
Author(s):  
Megan C. Neville ◽  
Tetsuya Nojima ◽  
Elizabeth Ashley ◽  
Darren J. Parker ◽  
John Walker ◽  
...  
Keyword(s):  
Nervous System ◽  
Sexually Dimorphic ◽  
Male Specific

Regulation of gene expression in the nervous system

2008 ◽  
Vol 414 (3) ◽  
pp. 327-341 ◽  
Author(s):  
Lezanne Ooi ◽  
Ian C. Wood
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Transcription Factors ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Gene Regulatory

The nervous system contains a multitude of cell types which are specified during development by cascades of transcription factors acting combinatorially. Some of these transcription factors are only active during development, whereas others continue to function in the mature nervous system to maintain appropriate gene-expression patterns in differentiated cells. Underpinning the function of the nervous system is its plasticity in response to external stimuli, and many transcription factors are involved in regulating gene expression in response to neuronal activity, allowing us to learn, remember and make complex decisions. Here we review some of the recent findings that have uncovered the molecular mechanisms that underpin the control of gene regulatory networks within the nervous system. We highlight some recent insights into the gene-regulatory circuits in the development and differentiation of cells within the nervous system and discuss some of the mechanisms by which synaptic transmission influences transcription-factor activity in the mature nervous system. Mutations in genes that are important in epigenetic regulation (by influencing DNA methylation and post-translational histone modifications) have long been associated with neuronal disorders in humans such as Rett syndrome, Huntington's disease and some forms of mental retardation, and recent work has focused on unravelling their mechanisms of action. Finally, the discovery of microRNAs has produced a paradigm shift in gene expression, and we provide some examples and discuss the contribution of microRNAs to maintaining dynamic gene regulatory networks in the brain.

scholarly journals SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Neurological Manifestations ◽  
Wide Range ◽  
Inflammatory State ◽  
Acute Polyneuropathy ◽  
The Central Nervous System ◽  
The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

Sign in / Sign up

Export Citation Format

Share Document