Time-resolved morphological and transcriptomic characterization of early enteric neuron subtype emergence in chick

Area of Science:

• Developmental biology
• Neuroscience
• Genetics

Background:

• The genetic programs governing the development of the enteric nervous system (ENS) and its complex architecture are not well understood.
• The ENS controls gut function, and its proper development is essential for health.

Purpose of the Study:

• To elucidate the genetic programs and cellular dynamics underlying enteric nervous system development.
• To identify conserved molecular mechanisms of enteric circuit wiring across species.

Main Methods:

• Utilized chick embryos for whole gut three-dimensional (3D) imaging and single-nucleus transcriptomics.
• Performed time-resolved analyses of neuronal subtype development and gene expression.
• Conducted cross-species comparisons with human and mouse embryonic data.

Main Results:

• Observed dynamic axon network growth, characterized by increased axon density and diversified spatial orientation.
• Correlated observed morphological changes with cell-state transitions and specific axon guidance gene expression.
• Identified conserved enteric lineage trajectories and species-specific axon guidance programs across chick, human, and mouse embryos.
• Demonstrated that manipulating conserved networks (DSCAM, ISLR2) in chick whole gut cultures altered enteric axon patterns.

Conclusions:

• The study provides a time-resolved molecular and morphological atlas of early enteric nervous system development.
• Revealed conserved genetic networks and cell-state dynamics critical for enteric circuit formation across vertebrates.
• Established a robust experimental paradigm for studying human enteric neurodevelopmental disorders.