Retinoic Acid Inhibition Alters Intestinal Composition in Zebrafish: A Non-genetic Model to Study Hirschsprung...

Area of Science:

• Developmental Biology
• Gastroenterology
• Immunology

Background:

• Retinoic acid (RA) is essential for enteric nervous system (ENS) development.
• The specific roles of RA on non-neuronal intestinal cells are not fully understood.
• Zebrafish serve as a model to study RA's impact on intestinal composition and Hirschsprung disease (HSCR).

Purpose of the Study:

• To investigate the effects of RA inhibition on intestinal cell composition in zebrafish.
• To compare RA inhibition effects with a ret mutant HSCR model.
• To elucidate the distinct roles of RA and Ret signaling in intestinal development.

Main Methods:

• Zebrafish larvae were treated with diethylaminobenzaldehyde (DEAB), a RA synthesis inhibitor.
• Single-cell RNA sequencing was used to analyze intestinal cell composition.
• DEAB-treated zebrafish were compared to wildtype and a ret mutant HSCR model.

Main Results:

• RA inhibition reduced ENS cell numbers and altered non-neuronal populations, including increased epithelial cells and decreased immune cells.
• Inflammatory pathways were suppressed, and myofibroblast numbers increased, suggesting potential fibrosis.
• While both RA inhibition and ret mutation affected non-neuronal cells, the specific changes differed, highlighting distinct signaling roles.

Conclusions:

• RA plays a critical role in maintaining intestinal structure and immune homeostasis.
• Understanding both neuronal and non-neuronal cell dynamics is vital for HSCR research.
• Zebrafish models provide valuable insights into RA's complex influence on intestinal development.