Biology subjects

Melancon, E.

Publications and source records attributed to Melancon, E..

4 recordsLinked to original sources

bioRxiv2022

A mucin-regulated adhesin determines the intestinal biogeography and inflammatory character of a bacterial symbiont.

In a healthy gut, microbes are often aggregated with host mucus, yet the molecular basis for this organization and its impact on intestinal health are unclear. Mucus is a viscous physical barrier separating resident microbes from epithelia, but also provides glycan cues that regulate microbial behaviors. Using experimental evolution, we discovered a mucin-sensing pathway in an Aeromonas symbiont of zebrafish, Aer01. In response to the mucin-associated glycan N-acetylglucosamine, a sensor kinase regulates expression of a mucin-binding adhesin we named MbpA. When MbpA is disrupted, Aer01 colonizes to normal levels, but is largely planktonic and elicits increased intestinal inflammation, traits which are reversed by increasing cell surface MpbA. MbpA-like adhesins are common in human-associated bacteria and expression of an Akkermansia muciniphila MbpA-like adhesin in MbpA-deficient Aer01 restored lumenal aggregation and reversed its pro-inflammatory character. Our work demonstrates how resident bacteria use mucin glycans to modulate behaviors congruent with host health.

microbiology↗

bioRxiv2022

GLOBAL HOST RESPONSES TO THE MICROBIOTA AT SINGLE CELL RESOLUTION IN GNOTOBIOTIC ZEBRAFISH

Resident microbes are a feature of vertebrate animals that influence diverse aspects of their biology from tissue development to metabolism. Here we describe transcriptional responses to the microbiota across all the cells of a model developing vertebrate, the larval zebrafish. By performing single cell transcriptomic analysis of whole germ free and conventionalized larvae, we show that the impacts of the microbiota are sensed by all major organ systems but that responses are highly specific to different cell types. The presence of microbiota stimulates the expansion of progenitor-like cells in epithelial tissues and increases proliferation gene expression in progenitor-like cell populations of the immune and nervous systems. Across many cell types, including enterocytes, immune cells, and neurons, the microbiota upregulates expression of genes involved in microbial responses, cell type-specific activities, and cell type-specific deployment of ATP metabolism genes. These combined transcriptional patterns demonstrate how the microbiota simultaneously modulate cellular immune and metabolic programs. The impacts of the microbiota on tissue development are illustrated by the exocrine pancreas, which in the absence of the microbiota is smaller and composed of uniformly differentiated acinar cells. The presence of the microbiota results in exocrine pancreas enlargement and heterogeneous cellular expression of digestive enzyme and secretion genes, demonstrating how the microbiota promotes plasticity in tissue development and function. This single cell transcriptional dataset demonstrates the impacts of the microbiota on vertebrate development across the body and provides a foundation for dissecting cell type specific responses to microbial consortia members or molecules. SummaryAnimal development proceeds in the presence of intimate microbial associations, but the extent to which different host cells across the body respond to resident microbes remains to be fully explored. Using the vertebrate model organism, the larval zebrafish, we assessed transcriptional responses to the microbiota across the entire body at single cell resolution. We find that cell types across the body, not limited to tissues at host-microbe interfaces, respond to the microbiota. Responses are cell-type specific, but across many tissues the microbiota enhances cell proliferation, increases metabolism, and stimulates a diversity of cellular activities, revealing roles for the microbiota in promoting developmental plasticity. This work provides a resource for exploring transcriptional responses to the microbiota across all cell types of the vertebrate body and generating new hypotheses about the interactions between vertebrate hosts and their microbiota.

developmental biology↗

bioRxiv2018

Epigenetic factors coordinate intestinal development

Intestinal epithelium development depends on epigenetic modifications, but whether that is also the case for other intestinal tract cell types remains unclear. We found that functional loss of a DNA methylation machinery component, ubiquitin-like protein containing PHD and RING finger domains 1 (uhrf1), leads to reduced enteric neuron number, changes in neuronal morphology, and severe intestinal smooth muscle disruption. Genetic chimeras revealed that Uhrf1 functions both cell-autonomously in enteric neuron progenitors and cell-non-autonomously in surrounding intestinal cells. Uhrf1 recruits the DNA methyltransferase Dnmt1 to unmethylated DNA during replication. Dnmt1 is also expressed in enteric neuron and smooth muscle progenitors. dnmt1 mutants show a strong reduction in enteric neuron number and disrupted intestinal smooth muscle. Because dnmt1;uhrf1 double mutants have a similar phenotype to dnmt1 and uhrf1 single mutants, Dnmt1 and Uhrf1 must function together during enteric neuron and intestinal muscle development. This work shows that genes controlling epigenetic modifications are important in coordinating intestinal tract development, provides the first demonstration that these genes are important in ENS development, and advances uhrf1 and dnmt1 as potential new Hirschsprung disease candidates.\n\nSummaryThis work provides evidence that DNA methylation factors are important in all cell types that contribute to development of a functional intestine.

developmental biology↗

bioRxiv2017

Image velocimetry and spectral analysis enable quantitative characterization of larval zebrafish gut motility

Summary StatementWe present a new image analysis technique using image velocimetry and spectral analysis that returns quantitative measures of gut contraction strength, frequency, and wave speed that can be used to study gut motility and other cellular movements.\n\nAbstractNormal gut function requires rhythmic and coordinated movements that are affected by developmental processes, physical and chemical stimuli, and many debilitating diseases. The imaging and characterization of gut motility, especially regarding periodic, propagative contractions driving material transport, are therefore critical goals. Whereas previous image analysis approaches have successfully extracted properties related to temporal frequency of motility modes, robust measures of contraction magnitude remain elusive. We developed a new image analysis method based on image velocimetry and spectral analysis that reveals temporal characteristics such as frequency and wave propagation speed, while also providing quantitative measures of the amplitude of gut motions. We validate this approach using several challenges to larval zebrafish, imaged with differential interference contrast microscopy. Both acetylcholine exposure and feeding increase frequency and amplitude of motility. Larvae lacking enteric nervous system gut innervation show the same average motility frequency, but reduced and less variable amplitude compared to wild-types. Our image analysis approach enables insights into gut dynamics in a wide variety of developmental and physiological contexts and can also be extended to analyze other types of cell movements.

developmental biology↗