Dataset Information

Modular Organization of Cis-regulatory Control Information of Neurotransmitter Pathway Genes in Caenorhabditis elegans.

ABSTRACT: We explore here the cis-regulatory logic that dictates gene expression in specific cell types in the nervous system. We focus on a set of eight genes involved in the synthesis, transport, and breakdown of three neurotransmitter systems: acetylcholine (unc-17 /VAChT, cha-1 /ChAT, cho-1 /ChT, and ace-2 /AChE), glutamate (eat-4 /VGluT), and γ-aminobutyric acid (unc-25 /GAD, unc-46 /LAMP, and unc-47 /VGAT). These genes are specifically expressed in defined subsets of cells in the nervous system. Through transgenic reporter gene assays, we find that the cellular specificity of expression of all of these genes is controlled in a modular manner through distinct cis-regulatory elements, corroborating the previously inferred piecemeal nature of specification of neurotransmitter identity. This modularity provides the mechanistic basis for the phenomenon of "phenotypic convergence," in which distinct regulatory pathways can generate similar phenotypic outcomes (i.e., the acquisition of a specific neurotransmitter identity) in different neuron classes. We also identify cases of enhancer pleiotropy, in which the same cis-regulatory element is utilized to control gene expression in distinct neuron types. We engineered a cis-regulatory allele of the vesicular acetylcholine transporter, unc-17 /VAChT, to assess the functional contribution of a "shadowed" enhancer. We observed a selective loss of unc-17 /VAChT expression in one cholinergic pharyngeal pacemaker motor neuron class and a behavioral phenotype that matches microsurgical removal of this neuron. Our analysis illustrates the value of understanding cis-regulatory information to manipulate gene expression and control animal behavior.

SUBMITTER: Serrano-Saiz E

PROVIDER: S-EPMC7337081 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Modular Organization of Cis-regulatory Control Information of Neurotransmitter Pathway Genes in Caenorhabditis elegans.

Serrano-Saiz Esther E Gulez Burcu B Pereira Laura L Gendrel Marie M Kerk Sze Yen SY Vidal Berta B Feng Weidong W Wang Chen C Kratsios Paschalis P Rand James B JB Hobert Oliver O

Genetics 20200522 3

We explore here the cis-regulatory logic that dictates gene expression in specific cell types in the nervous system. We focus on a set of eight genes involved in the synthesis, transport, and breakdown of three neurotransmitter systems: acetylcholine (unc-17/VAChT, cha-1/ChAT, cho-1/ChT, and ace-2/AChE), glutamate (eat-4/VGluT), and γ-aminobutyric acid (unc-25/GAD, unc-46/LAMP, and unc-47< ...[more]

PMID: 32444379

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Project description:The connectome, or the entire connectivity of a neural system represented by a network, ranges across various scales from synaptic connections between individual neurons to fibre tract connections between brain regions. Although the modularity they commonly show has been extensively studied, it is unclear whether the connection specificity of such networks can already be fully explained by the modularity alone. To answer this question, we study two networks, the neuronal network of Caenorhabditis elegans and the fibre tract network of human brains obtained through diffusion spectrum imaging. We compare them to their respective benchmark networks with varying modularities, which are generated by link swapping to have desired modularity values. We find several network properties that are specific to the neural networks and cannot be fully explained by the modularity alone. First, the clustering coefficient and the characteristic path length of both C. elegans and human connectomes are higher than those of the benchmark networks with similar modularity. High clustering coefficient indicates efficient local information distribution, and high characteristic path length suggests reduced global integration. Second, the total wiring length is smaller than for the alternative configurations with similar modularity. This is due to lower dispersion of connections, which means each neuron in the C. elegans connectome or each region of interest in the human connectome reaches fewer ganglia or cortical areas, respectively. Third, both neural networks show lower algorithmic entropy compared with the alternative arrangements. This implies that fewer genes are needed to encode for the organization of neural systems. While the first two findings show that the neural topologies are efficient in information processing, this suggests that they are also efficient from a developmental point of view. Together, these results show that neural systems are organized in such a way as to yield efficient features beyond those given by their modularity alone.

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Dataset Information

Modular Organization of Cis-regulatory Control Information of Neurotransmitter Pathway Genes in Caenorhabditis elegans.

Publications

Modular Organization of <i>Cis</i>-regulatory Control Information of Neurotransmitter Pathway Genes in <i>Caenorhabditis elegans</i>.

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