ArticleFrontiers in cell and developmental biology2025
Cecal growth factors promote enteric neurosphere formation and hindgut colonization in the avian model.
Article in Frontiers in cell and developmental biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Plasticity, injury-induced reprogramming, and translational applications of Schwann cells in neural regeneration.Frontiers in cellular neuroscience · 2026Review
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10 authors.
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Abstract
Introduction: The enteric nervous system (ENS) originates from neural crest cells (NCC) that migrate along the developing gut and differentiate into enteric neurons and glial cells. Disruption of ENS development leads to neurointestinal disorders, such as Hirschsprung disease (HSCR), characterized by aganglionic segments in the distal colon. ENS-derived stem cells (ENSCs), capable of forming multipotent neurospheres, have shown great promise for cell-based therapies. However, optimizing the cell culture conditions and understanding the molecular signals that regulate ENSC development remain unclear. Given the conserved developmental interactions between NCCs and the gut mesenchymal environment in mammals and birds, the avian embryo provides a valuable model for investigating ENS development. Methods: In this study, we developed and characterized an avian model system for generating enteric neurospheres from transgenic Results: Addition of GDNF, WNT11, endothelin-3, and the BMP inhibitor Noggin (GWEN medium) resulted in significantly larger and more numerous neurospheres compared to control cultures. Immunostaining showed that GWEN-treated neurospheres contained abundant SOX10+ glial precursors, HU + neurons, and SOX10+/PHOX2B+/HU- progenitors, indicating both differentiation and maintenance of stem cells. When plated on a fibronectin-coated surface in the presence of GDNF, cells from GWEN-treated neurospheres migrated a longer distance and extended more βIII-tubulin + neurites than controls, demonstrating enhanced neurogenic potential. Using Conclusion: These findings support the neurosphere-forming potential of avian ENSCs and identify ceca-derived signals (GDNF, WNT11, ET-3) and Noggin as potent regulators of ENS progenitor maintenance and differentiation.
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