Biology subjects

Sural, S.

Publications and source records attributed to Sural, S..

6 recordsLinked to original sources

bioRxiv2026

A conserved C. elegans zinc finger-homeodomain protein, ZFH-2, continuously required for structural integrity and function of alimentary tract and gonad

An unusually large transcription factor arose at the base of bilaterian evolution through domain shuffling that recombined many copies of two distinct DNA binding domains, C2H2-type zinc fingers and homeodomains. The function of this deeply conserved type of protein remains poorly characterized. We describe here the complete and complex expression pattern of its sole C. elegans representative, ZFH-2, throughout development and adulthood. We show that animals lacking this protein display defects in proper alimentary tract formation and starve to death in the first larval stage with an apparent inability to ingest food. Conditional removal of ZFH-2 at post-developmental stages reveals a continuous function of this protein in enabling food ingestion and demonstrates additional essential functions for the formation of other, postembryonically generated tubular structures. Even though ZFH-2 is broadly expressed throughout the nervous system, we detected no obvious defects in neuronal development or function in zfh-2 null mutants. Genome-engineered alleles indicate that while a large part of the protein is dispensable, at least a subset of the homeodomains are critical determinants for the essential functions of this protein.

developmental biology↗

bioRxiv2025

PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons of C. elegans

FoxA transcription factors pattern gut tissue across animal phylogeny. Beyond their early patterning function, little is known about whether they control the terminal differentiation and/or function of the fully mature enteric nervous system, the intrinsic nervous system of the gut. We show here that the expression and function of the sole C. elegans FoxA homolog, PHA-4, reaches beyond its previously described pioneer factor roles in patterning the foregut. Through the engineering of neuron-specific cis-regulatory alleles, Cre-mediated cell-specific knockouts and degron-mediated, temporally controlled PHA-4/FoxA removal in postmitotic neurons, we found that PHA-4/FoxA is required not only to initiate the terminal differentiation program of foregut-associated enteric neurons, but also to maintain their functional properties throughout the life of the animal. Moreover, we discovered novel sites of expression of PHA-4/FoxA in extrapharyngeal enteric neurons that innervate the hindgut (AVL and DVB), a GABAergic interneuron that controls foregut function during sleep (RIS), and a peptidergic neuron, PVT, which we implicate here in controlling defecation behavior. We show that while PHA-4/FoxA is not required for the developmental specification of AVL, DVB, RIS, and PVT, it is required to enable these neurons to control enteric functions. Taken together, pha-4 is the only transcription factor known to date that is expressed in and required for the proper function of all distinct types of enteric neurons in a nervous system.

neuroscience↗

bioRxiv2025

Gut epithelium modifies enteric behaviors during nutritional adversity via distinct peptidergic signaling axes

Interorgan signaling events are emerging as key regulators of behavioral plasticity. The foregut and hindgut circuits of the C. elegans enteric nervous system (ENS) control feeding and defecation behavior, respectively. Here we show that epithelial cells in the midgut integrate feeding state information to control these behavioral outputs by releasing distinct neuropeptidergic signals. In favorable conditions, insulin and non-insulin peptides released from midgut epithelia activate foregut and hindgut enteric neurons, respectively, to sustain normal feeding and defecation behavior. During food scarcity, altered insulin signaling from sensory neurons activates the transcription factor DAF-16/FoxO in midgut epithelia, which blocks both peptidergic signaling axes to the ENS by transcriptionally shutting down the intestinal neuropeptide secretion machinery. Our findings demonstrate that midgut epithelial cells act as integrators to relay internal state information to distinct parts of the enteric nervous system to control animal behavior.

neuroscience↗

bioRxiv2023

A neurotransmitter atlas of the nervous system of C.elegans males and hermaphrodites

Mapping neurotransmitter identities to neurons is key to understanding information flow in a nervous system. It also provides valuable entry points for studying the development and plasticity of neuronal identity features. In the C. elegans nervous system, neurotransmitter identities have been largely assigned by expression pattern analysis of neurotransmitter pathway genes that encode neurotransmitter biosynthetic enzymes or transporters. However, many of these assignments have relied on multicopy reporter transgenes that may lack relevant cis-regulatory information and therefore may not provide an accurate picture of neurotransmitter usage. We analyzed the expression patterns of 16 CRISPR/Cas9-engineered knock-in reporter strains for all main types of neurotransmitters in C. elegans (glutamate, acetylcholine, GABA, serotonin, dopamine, tyramine, and octopamine) in both the hermaphrodite and the male. Our analysis reveals novel sites of expression of these neurotransmitter systems within both neurons and glia, as well as non-neural cells. The resulting expression atlas defines neurons that may be exclusively neuropeptidergic, substantially expands the repertoire of neurons capable of co-transmitting multiple neurotransmitters, and identifies novel neurons that uptake monoaminergic neurotransmitters. Furthermore, we also observed unusual co-expression patterns of monoaminergic synthesis pathway genes, suggesting the existence of novel monoaminergic transmitters. Our analysis results in what constitutes the most extensive whole-animal-wide map of neurotransmitter usage to date, paving the way for a better understanding of neuronal communication and neuronal identity specification in C. elegans.

neuroscience↗

bioRxiv2020

DAF-16/FoxO and DAF-12/VDR control cellular plasticity both cell-autonomously and via interorgan signaling

Many cell types display the remarkable ability to alter their cellular phenotype in response to specific external or internal signals. Such phenotypic plasticity is apparent in the nematode C. elegans when adverse environmental conditions trigger entry into the dauer diapause stage. This entry is accompanied by structural, molecular and functional remodeling of a number of distinct tissue types of the animal, including its nervous system. The transcription factor effectors of three different hormonal signaling systems, the insulin-responsive DAF-16/FoxO transcription factor, the TGF{beta}-responsive DAF-3/SMAD transcription factor and the steroid nuclear hormone receptor, DAF-12/VDR, a homolog of the vitamin D receptor, were previously shown to be required for entering the dauer arrest stage, but their cellular and temporal focus of action for the underlying cellular remodeling processes remained incompletely understood. Through the generation of conditional alleles that allowed us to spatially and temporally control gene activity, we show here that all three transcription factors are not only required to initiate tissue remodeling upon entry into the dauer stage, as shown before, but are also continuously required to maintain the remodeled state. We show that DAF-3/SMAD is required in sensory neurons to promote and then maintain animal-wide tissue remodeling events. In contrast, DAF-16/FoxO or DAF-12/VDR act cell autonomously to control anatomical, molecular and behavioral remodeling events in specific cell types. Intriguingly, we also uncover non-cell autonomous function of DAF-16/FoxO and DAF-12/VDR in nervous system remodeling, indicating the presence of several insulin-dependent inter-organ signaling axes. Our findings provide novel perspectives on how hormonal systems control tissue remodeling.

genetics↗

bioRxiv2019

HSB-1 inhibition and HSF-1 overexpression trigger overlapping transcriptional changes to promote longevity in Caenorhabditis elegans

Heat shock factor 1 (HSF-1) is a component of the heat shock response pathway that is induced by cytoplasmic proteotoxic stress. In addition to its role in stress response, HSF-1 also acts as a key regulator of the rate of organismal aging. Overexpression of HSF-1 promotes longevity in C. elegans via mechanisms that remain less understood. Moreover, genetic ablation of a negative regulator of HSF-1, termed as heat shock factor binding protein 1 (HSB-1), results in hsf-1-dependent life span extension in animals. Here we show that in the absence of HSB-1, HSF-1 acquires increased DNA binding activity to its genomic target sequence. Using RNA-Seq to compare the gene expression profiles of the hsb-1 mutant and hsf-1 overexpression strains, we found that while more than 1,500 transcripts show [≥]1.5-fold upregulation due to HSF-1 overexpression, HSB-1 inhibition alters the expression of less than 500 genes in C. elegans. Roughly half of the differentially regulated transcripts in the hsb-1 mutant have altered expression also in hsf-1 overexpressing animals, with a strongly correlated fold-expression pattern between the two strains. In addition, genes that are upregulated via both HSB-1 inhibition and HSF-1 overexpression include numerous DAF-16 targets that have known functions in longevity regulation. This study identifies how HSB-1 acts as a specific regulator of the transactivation potential of HSF-1 in non-stressed conditions, thus providing a detailed understanding of the role of HSB-1/HSF-1 signaling pathway in transcriptional regulation and longevity in C. elegans.

genetics↗