A distinct transcriptome characterizes neural crest-derived cells at the migratory wavefront during enteric nervous...

Area of Science:

• Developmental biology
• Neuroscience
• Genetics

Background:

• Enteric nervous system (ENS) development depends on enteric neural crest-derived cells (ENCDCs).
• The molecular identity of highly migratory ENCDCs at the gut's leading edge (wavefront) is unknown.
• Understanding ENCDC behavior is crucial for ENS formation and function.

Purpose of the Study:

• To characterize the molecular profile of wavefront ENCDCs.
• To identify molecular mechanisms regulating ENCDC migration.
• To investigate the role of Dusp6 in ENS development.

Main Methods:

• Isolation and RNA sequencing of wavefront and trailing ENCDCs.
• Temporal modeling of gene expression data.
• Inhibition of DUSP6 and ERK signaling in mouse and chick models.

Main Results:

• Wavefront ENCDCs are transcriptionally distinct, immature, and exhibit a migratory gene expression profile.
• Wavefront ENCDCs lack neuronal/glial maturation markers, unlike trailing cells.
• Dusp6 is upregulated at the wavefront; its inhibition impairs hindgut colonization and ENCDC migration via ERK signaling.

Conclusions:

• Wavefront ENCDCs represent an immature, migratory progenitor population essential for ENS development.
• DUSP6-mediated ERK inhibition is a critical regulator of ENCDC migration.
• These findings provide insights into maintaining progenitor characteristics during ENS development.