Homeobox genes and the specification of neuronal identity

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(10), P. 627 - 636

Published: Aug. 26, 2021

Language: Английский

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Widespread employment of conserved C. elegans homeobox genes in neuronal identity specification

PLoS Genetics, Journal Year: 2022, Volume and Issue: 18(9), P. e1010372 - e1010372

Published: Sept. 30, 2022

Homeobox genes are prominent regulators of neuronal identity, but the extent to which their function has been probed in animal nervous systems remains limited. In nematode Caenorhabditis elegans, each individual neuron class is defined by expression unique combinations homeobox genes, prompting question whether indeed requires a gene for its proper identity specification. We present here progress addressing this extending previous mutant analysis family members and describing multiple examples different parts C. elegans system. To probe function, we make use number reporter tools, including novel multicolor transgene, NeuroPAL, permits simultaneous monitoring execution differentiation programs throughout entire Using these add characterization identifying defects 14 24 distinct classes that mostly unrelated location, lineage history. 12 had no ascribed them before, while other classes, extend combinatorial code transcription factors required specifying terminal programs. Furthermore, demonstrate particular lineage, homeotic transformations occur upon loss show result changes codes. Combining with past analyses, 113 118 now known require Such broad deployment indicates specification may be an ancestral feature systems.

Language: Английский

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Temporal transitions in the post-mitotic nervous system of Caenorhabditis elegans

Nature, Journal Year: 2021, Volume and Issue: 600(7887), P. 93 - 99

Published: Nov. 10, 2021

Language: Английский

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The enteric nervous system of the C. elegans pharynx is specified by the Sine oculis-like homeobox gene ceh-34

eLife, Journal Year: 2022, Volume and Issue: 11

Published: March 24, 2022

Overarching themes in the terminal differentiation of enteric nervous system, an autonomously acting unit animal systems, have so far eluded discovery. We describe here overall regulatory logic system nematode Caenorhabditis elegans that resides within foregut (pharynx) worm. A C. homolog Drosophila Sine oculis homeobox gene, ceh-34 , is expressed all 14 classes interconnected pharyngeal neurons from their birth throughout life time, but no other neuron type entire animal. Constitutive and temporally controlled removal shows required to initiate maintain type-specific program classes, including circuit assembly. Through additional genetic loss function analysis, we show each class, cooperates with different homeodomain transcription factors individuate distinct classes. Our analysis underscores critical role genes neuronal identity specification links them control assembly system. Together simplicity as well its by a homolog, our findings invite speculations about early evolution systems.

Language: Английский

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A set of hub neurons and non-local connectivity features support global brain dynamics in C. elegans

Current Biology, Journal Year: 2022, Volume and Issue: 32(16), P. 3443 - 3459.e8

Published: July 8, 2022

The wiring architecture of neuronal networks is assumed to be a strong determinant their dynamical computations. An ongoing effort in neuroscience therefore generate comprehensive synapse-resolution connectomes alongside brain-wide activity maps. However, the structure-function relationship, i.e., how anatomical connectome and dynamics relate each other on global scale, remains unsolved. Systematically, comparing graph features C. elegans with correlations nervous system-wide dynamics, we found that few local connectivity motifs mostly non-local such as triplet input similarities can predict functional relationships between neurons. Surprisingly, quantities connection strength amount common inputs do not improve these predictions, suggesting network's topology sufficient. We demonstrate hub neurons are key relevant features. Consistently, inhibition multiple specifically disrupts correlations. Thus, propose set provide an substrate for brain dynamics.

Language: Английский

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Caenorhabditis elegans sine oculis/SIX-type homeobox genes act as homeotic switches to define neuronal subtype identities

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(37)

Published: Sept. 6, 2022

The classification of neurons into distinct types reveals hierarchical taxonomic relationships that reflect the extent similarity between neuronal cell types. At base such taxonomies are cells very similar to one another but differ in a small number reproducible and select features. How members neuron class share many features instructed diversify subclasses? We show here six

Language: Английский

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Coordinated control of neuronal differentiation and wiring by sustained transcription factors

Science, Journal Year: 2022, Volume and Issue: 378(6626)

Published: Dec. 8, 2022

The large diversity of cell types in nervous systems presents a challenge identifying the genetic mechanisms that encode it. Here, we report nearly 200 distinct neurons Drosophila visual system can each be defined by unique combinations on average 10 continuously expressed transcription factors. We show targeted modifications this terminal selector code induce predictable conversions neuronal fates appear morphologically and transcriptionally complete. Cis-regulatory analysis open chromatin links one these genes to an upstream patterning factor specifies stem cells. Experimentally validated network models describe synergistic regulation downstream effectors selectors ecdysone signaling during brain wiring. Our results provide generalizable framework how specific are implemented postmitotic neurons.

Language: Английский

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Temporal transitions in the postembryonic nervous system of the nematode Caenorhabditis elegans: Recent insights and open questions

Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 142, P. 67 - 80

Published: June 7, 2022

After the generation, differentiation and integration into functional circuitry, post-mitotic neurons continue to change certain phenotypic properties throughout postnatal juvenile stages until an animal has reached a fully mature state in adulthood. We will discuss such changes context of nervous system nematode C. elegans, focusing on recent descriptions anatomical molecular that accompany postembryonic maturation neurons. summarize characterization genetic timer mechanisms control these temporal transitions or maturational changes, many but not all relate sexual animal. describe how temporal, spatial sex-determination pathways are intertwined sculpt emergence cell-type specific events. Finally, we lay out several unresolved questions should be addressed move field forward, both elegans vertebrates.

Language: Английский

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Neurogenesis in Caenorhabditis elegans

Genetics, Journal Year: 2024, Volume and Issue: 228(2)

Published: Aug. 21, 2024

Abstract Animals rely on their nervous systems to process sensory inputs, integrate these with internal signals, and produce behavioral outputs. This is enabled by the highly specialized morphologies functions of neurons. Neuronal cells share multiple structural physiological features, but they also come in a large diversity types or classes that give system its broad range plasticity. diversity, first recognized over century ago, spurred classification efforts based morphology, function, molecular criteria. Caenorhabditis elegans, precisely mapped at anatomical level, an extensive description most neurons, genetic amenability, has been prime model for understanding how neurons develop diversify mechanistic level. Here, we review gene regulatory mechanisms driving neurogenesis diversification neuron subclasses C. elegans. We discuss our current specification neuronal progenitors differentiation terms transcription factors involved ensuing changes expression chromatin landscape. The central theme emerged identity defined modules batteries are under control parallel yet interconnected mechanisms. focus how, achieve terminal identities, information along developmental lineages. Moreover, diversified postembryonically time-, sex-, activity-dependent manner. Finally, development can provide insights into evolution diversity.

Language: Английский

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Functional analysis of conserved C. elegans bHLH family members uncovers lifespan control by a peptidergic hub neuron

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(1), P. e3002979 - e3002979

Published: Jan. 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.

Language: Английский

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