Single-Nucleus Neuronal Transcriptional Profiling of MaleC. elegansUncovers Regulators of Sex-Specific and Sex-Shared Behaviors DOI Open Access
Katherine Morillo, Jonathan St. Ange, Yifei Weng

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

Summary Sexual differentiation of the nervous system causes differences in neuroanatomy, synaptic connectivity, and physiology. These sexually-dimorphic phenotypes ultimately translate into profound behavioral differences. C. elegans’ two sexes, XO males XX hermaphrodites, demonstrate neurobiology behavior. However, neuron class sex-specific transcriptomic differences, particularly at single-neuron level, that cause such phenotypic divergence remains understudied. Here, using single-nucleus RNA sequencing, we assessed compared adult male hermaphrodite elegans neuronal transcriptomes, identifying neurons, including previously-unannotated neurons. Sex-shared neurons displayed large expression with some classes clustering as distinct between sexes. Males express ∼100 male-specific GPCRs, largely limited to a subset We identified most highly-divergent functionally characterized sex-shared target, vhp-1, pheromone chemotaxis. Our data provide resource for discovering nervous-system-wide sex molecular basis behaviors.

Язык: Английский

Functional analysis of conserved C. elegans bHLH family members uncovers lifespan control by a peptidergic hub neuron DOI Creative Commons
G Robert Aguilar,

Berta Vidal,

Hongzhu Ji

и другие.

PLoS Biology, Год журнала: 2025, Номер 23(1), С. e3002979 - e3002979

Опубликована: Янв. 6, 2025

Throughout the animal kingdom, several members of basic helix-loop-helix (bHLH) family act as proneural genes during early steps nervous system development. Roles bHLH in specifying terminal differentiation postmitotic neurons have been less extensively studied. We analyze here function 5 Caenorhabditis elegans genes, falling into 3 phylogenetically conserved subfamilies, which are continuously expressed a very small number central system. show (a) that 2 orthologs vertebrate bHLHe22/e23 called hlh-17 and hlh-32, redundantly to specify identity single head interneuron class (AUA), well an individual motor neuron (VB2); (b) PTF1a ortholog hlh-13 acts selector control sole octopaminergic C. elegans, RIC; (c) NHLH1/2 hlh-15 controls peptidergic AVK class, known neuropeptidergic signaling hub animal. Strikingly, through null mutant analysis cell-specific rescue experiments, we find loss hlh-15/NHLH resulting abrogation neuropeptide secretion from these causes substantially extended lifespan animal, propose be akin hypothalamic vertebrates. Our functional reveals themes gene complementary earlier lineage specification roles other members. However, such late functions much more sparsely employed by transcription factor family, compared broadly homeodomain family.

Язык: Английский

Процитировано

0
The forkhead transcription factor FKH-7/FOXP acts in chemosensory neurons to regulate developmental decision-making DOI Creative Commons
Cynthia M. Chai, Seth R. Taylor, Carsten H. Tischbirek

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

SUMMARY Autism is a complex neurodevelopmental disorder with many associated genetic factors, including the forkhead transcription factor FOXP1. Although FOXP1’s neuronal role well-studied, specific molecular consequences of different FOXP1 pathogenic variants in physiologically-relevant contexts are unknown. Here we ascribe first function to Caenorhabditis elegans FKH-7/FOXP, which acts two chemosensory neuron classes promote larval decision enter alternative, developmentally-arrested dauer life stage. We demonstrate that human can functionally substitute for C. FKH-7 these neurons and engineering analogous hypomorphic missense mutations endogenous fkh-7 locus also impairs developmental decision-making. In fkh-7/FOXP1 variant, single-cell transcriptomics identifies downregulated expression autism-associated kcnl-2/KCNN2 calcium-activated potassium channel serotonergic sensory neuron. Our findings establish novel framework linking evolutionarily-conserved genes deeper characterization variant-specific pathology at single resolution context decision-making paradigm.

Язык: Английский

Процитировано

0
Functional analysis of conserved C. elegans bHLH family members uncovers lifespan control by a peptidergic hub neuron DOI
G Robert Aguilar,

Berta Vidal,

Hongzhu Ji

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 16, 2024

ABSTRACT Throughout the animal kingdom, several members of basic helix-loop-helix (bHLH) family act as proneural genes during early steps nervous system development. Roles bHLH in specifying terminal differentiation postmitotic neurons have been less extensively studied. We analyze here function five C. elegans genes, falling into three phylogenetically conserved subfamilies, which are continuously expressed a very small number central system. show (a) that two orthologs vertebrate bHLHb4/b5 called hlh-17 and hlh-32, redundantly to specify identity single head interneuron (AUA), well an individual motor neuron (VB2), (b) PTF1a ortholog hlh-13 acts selector control sole octopaminergic class , RIC, (c) NHLH1/2 hlh-15 controls peptidergic AVK class, known neuropeptidergic signaling hub animal. Strikingly, through null mutant analysis cell-specific rescue experiments, we find loss hlh-15/NHLH resulting abrogation neuropeptide secretion causes substantially expanded lifespan animal, revealing unanticipated impact central, regulating lifespan, propose be akin hypothalamic vertebrates. Taken together, our functional reveals themes gene complementary earlier lineage specification roles other members. However, such late functions much more sparsely employed by transcription factor family, compared broadly homeodomain family.

Язык: Английский

Процитировано

0
Neural Sequences Underlying Directed Turning inC. elegans DOI Creative Commons
Talya S. Kramer,

Flossie K. Wan,

Sarah Pugliese

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 11, 2024

Complex behaviors like navigation rely on sequenced motor outputs that combine to generate effective movement. The brain-wide organization of the circuits integrate sensory signals select and execute appropriate sequences is not well understood. Here, we characterize architecture neural control

Язык: Английский

Процитировано

0
NeuroSCAN: ExploringNeurodevelopment viaSpatiotemporalCollation ofAnatomicalNetworks DOI Creative Commons
Noelle L Koonce, Sarah E. Emerson, Dhananjay Bhaskar

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 27, 2024

Abstract Volume electron microscopy (vEM) datasets such as those generated for connectome studies allow nanoscale quantifications and comparisons of the cell biological features underpinning circuit architectures. Quantifications relationships in result rich multidimensional that benefit from data science approaches, including dimensionality reduction integrated graphical representations neuronal relationships. We developed NeuroSCAN, an online open-source platform bridges sophisticated graph analytics approaches with underlying connectome. analyze a series published C. elegans brain neuropils demonstrate how these facilitate across connectomes, catalyzing new insights on structure-function circuits their changes during development. NeuroSCAN is designed intuitive examination enabling synthesis knowledge high-level abstractions derived techniques to detailed identification abstractions.

Язык: Английский

Процитировано

0
Single-Nucleus Neuronal Transcriptional Profiling of MaleC. elegansUncovers Regulators of Sex-Specific and Sex-Shared Behaviors DOI Open Access
Katherine Morillo, Jonathan St. Ange, Yifei Weng

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

Summary Sexual differentiation of the nervous system causes differences in neuroanatomy, synaptic connectivity, and physiology. These sexually-dimorphic phenotypes ultimately translate into profound behavioral differences. C. elegans’ two sexes, XO males XX hermaphrodites, demonstrate neurobiology behavior. However, neuron class sex-specific transcriptomic differences, particularly at single-neuron level, that cause such phenotypic divergence remains understudied. Here, using single-nucleus RNA sequencing, we assessed compared adult male hermaphrodite elegans neuronal transcriptomes, identifying neurons, including previously-unannotated neurons. Sex-shared neurons displayed large expression with some classes clustering as distinct between sexes. Males express ∼100 male-specific GPCRs, largely limited to a subset We identified most highly-divergent functionally characterized sex-shared target, vhp-1, pheromone chemotaxis. Our data provide resource for discovering nervous-system-wide sex molecular basis behaviors.

Язык: Английский

Процитировано

0