Avian ceca are indispensable for hindgut enteric nervous system development.

Area of Science:

• Developmental biology
• Neuroscience
• Gastroenterology

Background:

• The enteric nervous system (ENS) innervates the gut and originates from enteric neural crest cells (ENCCs).
• Hirschsprung disease results from impaired ENCC migration, leading to an aganglionic distal bowel.
• ENCCs migrate craniocaudally along the developing intestine.

Purpose of the Study:

• To investigate the role of avian ceca in ENS development.
• To identify molecular mechanisms regulating ENCC migration and differentiation in the hindgut.
• To explore the function of the non-canonical Wnt signaling pathway in ENS formation.

Main Methods:

• Comparative transcriptome profiling of cecal buds and intercecal regions.
• RNA in situ hybridization to confirm gene expression.
• Organ culture of embryonic avian intestine to study WNT11 function.

Main Results:

• ENCC proliferation is highest as the wavefront passes through the ceca.
• Ceca removal causes hindgut aganglionosis, indicating their essential role.
• Non-canonical Wnt signaling, particularly WNT11, is upregulated in the ceca.
• WNT11 was found to inhibit enteric neuronal differentiation in organ cultures.

Conclusions:

• Avian ceca are vital for hindgut ENS development.
• Cecal WNT11 expression is critical for ENCC colonization of the hindgut.
• Non-canonical Wnt signaling plays a key role in regulating ENCC differentiation during ENS formation.