5-HT3 Signaling Alters Development of Sacral Neural Crest Derivatives That Innervate the Lower Urinary Tract

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• The autonomic nervous system, originating from neural crest cells, innervates visceral organs like the lower urinary tract.
• Pelvic ganglia, formed by sacral neural crest cells during fetal development, are essential for coordinated bladder function.
• The developmental processes governing pelvic ganglia neuronal diversity remain largely unexplored.

Purpose of the Study:

• To identify genes involved in pelvic ganglia neurogenesis.
• To investigate the role of serotonin signaling in the development of autonomic neurons.
• To understand the potential impact of developmental serotonin signaling on lower urinary tract function.

Main Methods:

• Transcriptome profiling of sacral neural crest cells and developing pelvic ganglia.
• In vitro cell culture to assess the effects of serotonin receptor 5-HT3 (5-hydroxytryptamine 3) signaling.
• Analysis of gene expression patterns, specifically focusing on 5-HT3 receptor subunits (Htr3a, Htr3b).

Main Results:

• The type 3 serotonin receptor (5-HT3) genes (Htr3a, Htr3b) were found to be enriched in developing pelvic ganglia.
• Htr3a is upregulated early in sacral neural crest progenitors and maintained in differentiating pelvic ganglia neurons.
• Disruption of 5-HT3 signaling in vitro altered neural crest cell differentiation, and its stimulation reduced neurite outgrowth in fetal pelvic ganglia.

Conclusions:

• Serotonin receptor 5-HT3 is a novel regulator of neural crest lineage diversification and peripheral nervous system neuronal maturation.
• This study provides a resource for analyzing signaling pathways in pelvic ganglia development.
• Perturbation of 5-HT3 signaling during gestation may affect later-life bladder function.