Genetic fate-mapping of tyrosine hydroxylase-expressing cells in the enteric nervous system

Background During development of the enteric nervous system, a subpopulation of enteric neuron precursors transiently expresses catecholaminergic properties. The progeny of these transiently catecholaminergic (TC) cells have not been fully characterized. Methods We combined in vivo Cre-lox-based genetic fate-mapping with phenotypic analysis to fate-map enteric neuron subtypes arising from tyrosine hydroxylase (TH)-expressing cells. Key Results Less than 3% of the total (Hu+) neurons in the myenteric plexus of the small intestine of adult mice are generated from transiently TH-expressing cells. Around 50% of the neurons generated from transiently TH-expressing cells are calbindin neurons, but their progeny also include calretinin, neurofilament-M, and serotonin neurons. However, only 30% of the serotonin neurons and small subpopulations (<10%) of the calbindin, calretinin, and neurofilament-M neurons are generated from TH-expressing cells; only 0.2% of nitric oxide synthase neurons arise from TH-expressing cells. Conclusions & Inferences Transiently, catecholaminergic cells give rise to subpopulations of multiple enteric neuron subtypes, but the majority of each of the neuron subtypes arises from non-TC cells.