Time-resolved morphological and transcriptomic characterization of early enteric neuron subtype emergence in chick
Abstract
The genetic programs directing nascent enteric nervous circuits and their unique architecture remain poorly characterized. To gain insight, we combined manipulations in the chick embryo model, whole gut three-dimensional (3D) imaging, and single-nucleus transcriptomics at very short intervals for time-resolved analyses of neuronal subtype trajectories. In imaging, we found highly dynamic axon network growth, with rapid increase in axon density and spatial orientation diversification. At transcriptomic levels, we correlated these changes to cell-state transitions with specific axon guidance gene sets. Cross-analyses with human and mouse embryo scRNAseq and expression profiles revealed globally conserved enteric lineage trajectories and subtypes specific axon guidance programs in all species. Finally, manipulation of DSCAM and ISLR2 evolutionary conserved networks in chick whole gut cultures altered enteric axon patterns, validating our paradigm and its applicability to advance current knowledge on human enteric circuit wiring.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (13)
Maëlys André
MeLis, CNRS UMR 5284, INSERM U1314, Université Lyon 1
Raphael Gury
MeLis, CNRS UMR 5284, INSERM U1314, Université Lyon 1
Maxime Lepetit
Bioinformatic Platform of the Labex Cortex, Université Lyon 1
Franck Boismoreau
MeLis, CNRS UMR 5284, INSERM U1314, Université Lyon 1
Muriel Bozon
MeLis, CNRS UMR 5284, INSERM U1314, Université Lyon 1
Jérémy Ganofsky
MeLis, CNRS UMR 5284, INSERM U1314, Université Lyon 1
Cassandre Heritier-Tellier
Bioinformatic Platform of the Labex Cortex, Université Lyon 1
Ingrid Plotton
Centre hospitalier universitaire de Lyon, laboratoire de biochimie et biologie moléculaire, Université Lyon 1
Rémi Duclaux-Loras
CarMEN laboratory, INSERM U1060, Institut national de recherche pour l’agriculture, l’alimentation et l’environnement 1397, 69495 Pierre Benite, France, Centre hospitalier universitaire de Lyon, Gastroenterology, Hepatology and Nutrition Unit, Université Lyon 1
Noël Peretti
CarMEN laboratory, INSERM U1060, Institut national de recherche pour l’agriculture, l’alimentation et l’environnement 1397, 69495 Pierre Benite, France, Centre hospitalier universitaire de Lyon, Gastroenterology, Hepatology and Nutrition Unit, Université Lyon 1
Guillaume Marcy
Bioinformatic Platform of the Labex Cortex, Université Lyon 1
Valérie Castellani
MeLis, CNRS UMR 5284, INSERM U1314, Université Lyon 1
Julien Falk
MeLis, CNRS UMR 5284, INSERM U1314, Université Lyon 1