Diversification of molecularly defined myenteric neuron classes revealed by single-cell RNA sequencing

Area of Science:

• Neuroscience
• Developmental Biology
• Genomics

Background:

• The enteric nervous system (ENS) autonomously regulates intestinal functions through diverse neuron types.
• Understanding the full spectrum of enteric neuron diversity and their developmental origins is crucial but remains incomplete.

Purpose of the Study:

• To establish a comprehensive molecular taxonomy of enteric neuron classes in the mouse small intestine.
• To elucidate the developmental principles governing enteric neuron diversification.

Main Methods:

• Single-cell RNA sequencing of neurons from the mouse small intestine's myenteric plexus.
• Transcriptome analysis of the embryonic ENS.
• Identification of cell-cell communication features and histochemical markers.

Main Results:

• Defined a molecular taxonomy of 12 distinct enteric neuron classes.
• Uncovered a novel developmental principle: initial binary neurogenic branching followed by postmitotic differentiation for other neuron types.
• Identified key transcriptional regulators, including Pbx3, involved in neuronal fate transitions.

Conclusions:

• Provides a foundational molecular and conceptual resource for studying ENS circuits.
• Enables prediction of regulators for directed differentiation of specific enteric neuron classes.
• Advances understanding of neuronal diversification in the developing nervous system.