scholarly journals Sexually dimorphic differentiation of a C. elegans hub neuron is cell-autonomously controlled by a conserved transcription factor

2016 ◽  
Author(s):  
Esther Serrano-Saiz ◽  
Meital Oren-Suissa ◽  
Emily A. Bayer ◽  
Oliver Hobert
Keyword(s):  
Transcription Factor ◽  
Glutamate Transporter ◽  
Sexually Dimorphic ◽  
Neuronal Function ◽  
Sexual Dimorphisms ◽  
C Elegans ◽  
Cellular Specificity ◽  
Male Specific ◽  
The Brain ◽  
Canonical Pattern

SUMMARYFunctional and anatomical sexual dimorphisms in the brain are either the result of cells that are generated only in one sex, or a manifestation of sex-specific differentiation of neurons present in both sexes. The PHC neurons of the nematode C. elegans differentiate in a strikingly sex-specific manner. While in hermaphrodites the PHC neurons display a canonical pattern of synaptic connectivity similar to that of other sensory neurons, PHC differentiates into a densely connected hub sensory/interneuron in males, integrating a large number of male-specific synaptic inputs and conveying them to both male-specific and sex-shared circuitry. We describe that the differentiation into such a hub neuron involves the sex-specific scaling of several components of the synaptic vesicle machinery, including the vesicular glutamate transporter eat-4/VGLUT, induction of neuropeptide expression, changes in axonal projection morphology and a switch in neuronal function. We demonstrate that these molecular and anatomical remodeling events are controlled cell-autonomously by the phylogenetically conserved Doublesex homolog dmd-3, which is both required and sufficient for sex-specific PHC differentiation. Cellular specificity of dmd-3 action is ensured by its collaboration with non-sex specific terminal selector-type transcription factors whereas sex-specificity of dmd-3 action is ensured by the hermaphrodite-specific master regulator of hermaphroditic cell identity, the Gli-like transcription factor tra-1, which transcriptionally represses dmd-3 in hermaphrodite PHC. Taken together, our studies provide mechanistic insights into how neurons are specified in a sexually dimorphic manner.

scholarly journals SNPC-1.3 is a sex-specific transcription factor that drives male piRNA expression in C. elegans

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Charlotte P Choi ◽  
Rebecca J Tay ◽  
Margaret R Starostik ◽  
Suhua Feng ◽  
James J Moresco ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Ectopic Expression ◽  
Sexually Dimorphic ◽  
Small Nuclear Rna ◽  
Germline Development ◽  
C Elegans ◽  
Male Germline ◽  
Nuclear Rna ◽  
Specific Regulation ◽  
Male Specific

Piwi-interacting RNAs (piRNAs) play essential roles in silencing repetitive elements to promote fertility in metazoans. Studies in worms, flies, and mammals reveal that piRNAs are expressed in a sex-specific manner. However, the mechanisms underlying this sex-specific regulation are unknown. Here we identify SNPC-1.3, a male germline-enriched variant of a conserved subunit of the small nuclear RNA-activating protein complex, as a male-specific piRNA transcription factor in Caenorhabditis elegans. SNPC-1.3 colocalizes with the core piRNA transcription factor, SNPC-4, in nuclear foci of the male germline. Binding of SNPC-1.3 at male piRNA loci drives spermatogenic piRNA transcription and requires SNPC-4. Loss of snpc-1.3 leads to depletion of male piRNAs and defects in male-dependent fertility. Furthermore, TRA-1, a master regulator of sex determination, binds to the snpc-1.3 promoter and represses its expression during oogenesis. Loss of TRA-1 targeting causes ectopic expression of snpc-1.3 and male piRNAs during oogenesis. Thus, sexually dimorphic regulation of snpc-1.3 expression coordinates male and female piRNA expression during germline development.

scholarly journals Decoding Sex Differences in the Brain, One Worm at a Time

2018 ◽  
Vol 2 (3) ◽  
pp. 76-80 ◽  
Author(s):  
Chen Wang
Keyword(s):  
Sex Differences ◽  
Transcription Factors ◽  
Model Organism ◽  
Basic Research ◽  
Cellular Level ◽  
Sexually Dimorphic ◽  
Sexual Dimorphisms ◽  
C Elegans ◽  
Genetic Technologies ◽  
The Brain

Sex differences in the brain are prominent features across the animal kingdom. Understanding the anatomical and regulatory mechanisms behind these differences is critical for both explaining sexually dimorphic behaviors and developing sex-targeted treatments for neurological disorders. Clinical studies considering sex biases and basic research on animal models have provided much evidence for the existence of sex differences in the brain and, in a larger sense, sexual dimorphisms in the nervous system. However, due to the complexity of structure and dimorphic behaviors, it is yet unclear precisely how neuronal sexual dimorphisms are regulated on a molecular or cellular level. This commentary reviews available tools for investigating sexual dimorphisms using a simple model organism, the roundworm Caenorhabditis elegans ( C. elegans), which enables one to study gene regulation at single-cell resolution with a number of cutting-edge molecular and genetic technologies. I highlight the doublesex/mab-3 family of transcription factors, first discovered in invertebrates, and their roles in a potentially universal regulatory mechanism underlying neuronal sexual dimorphisms. Studies of these transcription factors using C. elegans, fruit flies, and vertebrates will promote our understanding of fundamental mechanisms behind sex differences in the brain.

scholarly journals Sexually Dimorphic Differentiation of a C. elegans Hub Neuron Is Cell Autonomously Controlled by a Conserved Transcription Factor

2017 ◽  
Vol 27 (2) ◽  
pp. 199-209 ◽  
Author(s):  
Esther Serrano-Saiz ◽  
Meital Oren-Suissa ◽  
Emily A. Bayer ◽  
Oliver Hobert
Keyword(s):  
Transcription Factor ◽  
Sexually Dimorphic ◽  
C Elegans

scholarly journals Visualizing the organization and differentiation of the male-specific nervous system of C. elegans

2021 ◽  
Author(s):  
Tessa Tekieli ◽  
Eviatar Yemini ◽  
Amin Nejatbakhsh ◽  
Erdem Varol ◽  
Robert W Fernandez ◽  
...  
Keyword(s):  
Nervous System ◽  
Just In Time ◽  
Differentiation Markers ◽  
C Elegans ◽  
Larval Stages ◽  
Fourth Larval Stage ◽  
Developmental Patterning ◽  
Male Specific ◽  
Cluster Gene ◽  
The Brain

Sex differences in the brain are prevalent throughout the animal kingdom and particularly well appreciated in the nematode C. elegans. While 294 neurons are shared between the two sexes, the nervous system of the male contains an additional 93 male-specific neurons, most of which have received very little attention so far. To make these neurons amenable for future study, we describe here how a multicolor, multipromoter reporter transgene, NeuroPAL, is capable of visualizing the distinct identities of all male specific neurons. We used this tool to visualize and characterize a number of features of the male-specific nervous system. We provide several proofs of concept for using NeuroPAL to identify the sites of expression of gfp-tagged reporter genes. We demonstrate the usage of NeuroPAL for cellular fate analysis by analyzing the effect of removal of developmental patterning genes, including a HOX cluster gene (egl-5), a miRNA (lin-4) and a proneural gene (lin-32/Ato), on neuronal identity acquisition within the male-specific nervous system. We use NeuroPAL and its intrinsic cohort of more than 40 distinct differentiation markers to show that, even though male-specific neurons are generated throughout all four larval stages, they execute their terminal differentiation program in a coordinated manner in the fourth larval stage that is concomitant with male tale retraction. This wave of differentiation couples neuronal maturation programs with the appearance of sexual organs. We call this wave 'just-in-time' differentiation by its analogy to the mechanism of 'just-in-time' transcription of metabolic pathway genes.

scholarly journals SNPC-1.3 is a sex-specific transcription factor that drives male piRNA expression in C. elegans

2020 ◽  
Author(s):  
Charlotte P. Choi ◽  
Rebecca J. Tay ◽  
Margaret R. Starostik ◽  
Suhua Feng ◽  
James J. Moresco ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Complex ◽  
Ectopic Expression ◽  
Germline Development ◽  
Male And Female ◽  
C Elegans ◽  
The Core ◽  
Specific Manner ◽  
Specific Regulation ◽  
Male Specific

ABSTRACTPiwi-interacting RNAs (piRNAs) play essential roles in silencing repetitive elements to promote fertility in metazoans. Studies in worms, flies, and mammals reveal that piRNAs are expressed in a sex-specific manner. However, the mechanisms underlying this sex-specific regulation are unknown. Here we identify SNPC-1.3, a variant of a conserved subunit of the snRNA activating protein complex, as a male-specific piRNA transcription factor in C. elegans. Binding of SNPC-1.3 at male piRNA loci drives spermatogenic piRNA transcription and requires the core piRNA transcription factor SNPC-4. Loss of snpc-1.3 leads to depletion of male piRNAs and defects in male-dependent fertility. Furthermore, TRA-1, a master regulator of sex determination, binds to the snpc-1.3 promoter and represses its expression during oogenesis. Loss of TRA-1 targeting causes ectopic expression of snpc-1.3 and male piRNAs during oogenesis. Thus, sexual dimorphic regulation of snpc-1.3 coordinates male and female piRNA expression during germline development.

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 PDF-1 neuropeptide signaling regulates sexually dimorphic gene expression in shared sensory neurons of C. elegans

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Zoë A Hilbert ◽  
Dennis H Kim
Keyword(s):  
Sexually Dimorphic ◽  
Specific Expression ◽  
C Elegans ◽  
Pigment Dispersing Factor ◽  
Behavioral Decision ◽  
Specific Effects ◽  
Sexually Dimorphic Expression ◽  
Male Specific ◽  
Dimorphic Gene Expression ◽  
Dimorphic Expression

Sexually dimorphic behaviors are a feature common to species across the animal kingdom, however how such behaviors are generated from mostly sex-shared nervous systems is not well understood. Building on our previous work which described the sexually dimorphic expression of a neuroendocrine ligand, DAF-7, and its role in behavioral decision-making in C. elegans (Hilbert and Kim, 2017), we show here that sex-specific expression of daf-7 is regulated by another neuroendocrine ligand, Pigment Dispersing Factor (PDF-1), which has previously been implicated in regulating male-specific behavior (Barrios et al., 2012). Our analysis revealed that PDF-1 signaling acts sex- and cell-specifically in the ASJ neurons to regulate the expression of daf-7, and we show that differences in PDFR-1 receptor activity account for the sex-specific effects of this pathway. Our data suggest that modulation of the sex-shared nervous system by a cascade of neuroendocrine signals can shape sexually dimorphic behaviors.

scholarly journals Visualizing the organization and differentiation of the male-specific nervous system of C. elegans

Development ◽  
2021 ◽  
Author(s):  
Tessa Tekieli ◽  
Eviatar Yemini ◽  
Amin Nejatbakhsh ◽  
Chen Wang ◽  
Erdem Varol ◽  
...  
Keyword(s):  
Nervous System ◽  
Just In Time ◽  
Differentiation Markers ◽  
C Elegans ◽  
Larval Stages ◽  
Neuronal Identity ◽  
Fourth Larval Stage ◽  
Developmental Patterning ◽  
Male Specific ◽  
The Brain

Sex differences in the brain are prevalent throughout the animal kingdom and particularly well appreciated in the nematode C. elegans, where male animals contain a little studied set of 93 male-specific neurons. To make these neurons amenable for future study, we describe here how a multicolor reporter transgene, NeuroPAL, is capable of visualizing the distinct identities of all male specific neurons. We used NeuroPAL to visualize and characterize a number of features of the male-specific nervous system. We provide several proofs of concept for using NeuroPAL to identify the sites of expression of gfp-tagged reporter genes and for cellular fate analysis by analyzing the effect of removal of several developmental patterning genes on neuronal identity acquisition. We use NeuroPAL and its intrinsic cohort of more than 40 distinct differentiation markers to show that, even though male-specific neurons are generated throughout all four larval stages, they execute their terminal differentiation program in a coordinated manner in the fourth larval stage. This coordinated wave of differentiation, which we call “just-in-time" differentiation, couples neuronal maturation programs with the appearance of sexual organs.

scholarly journals A sexually dimorphic neuroendocrine cascade acts through shared sensory neurons to regulate behavior inC. elegans

2018 ◽  
Author(s):  
Zoë A. Hilbert ◽  
Dennis H. Kim
Keyword(s):  
Sexually Dimorphic ◽  
Animal Kingdom ◽  
Specific Expression ◽  
C Elegans ◽  
Pigment Dispersing Factor ◽  
Behavioral Decision ◽  
Specific Effects ◽  
Sexually Dimorphic Expression ◽  
Male Specific ◽  
Dimorphic Expression

ABSTRACTSexually dimorphic behaviors are observed in species across the animal kingdom, however the relative contributions of sex-specific and sex-shared nervous systems to such behaviors are not fully understood. Building on our previous work which described the sexually dimorphic expression of a neuroendocrine ligand, DAF-7, and its role in behavioral decision-making inC. elegans(Hilbert and Kim, 2017), we show here that sex-specific expression ofdaf-7is regulated by another neuroendocrine ligand, Pigment Dispersing Factor (PDF-1), which has previously been implicated in regulating male-specific behavior (Barrios et al., 2012). Our analysis revealed that PDF-1 acts sex- and cell-specifically in the ASJ neurons to regulate the expression ofdaf-7and we show that differences in the expression of the PDFR-1 receptor account for the sex-specific effects of this pathway. Our data suggest that modulation of the sex-shared nervous system by neuroendocrine signaling pathways can play a role in shaping sexually dimorphic behaviors.

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