Serotonergic neuroepithelial cells of the skin in developing zebrafish: morphology, innervation and oxygen-sensitive...

In teleost fish, O(2) chemoreceptors of the gills (neuroepithelial cells or NECs) initiate cardiorespiratory reflexes during hypoxia. In developing zebrafish, hyperventilatory and behavioural responses to hypoxia are observed before development of gill NECs, indicating that extrabranchial chemoreceptors mediate these responses in embryos. We have characterised a population of cells of the skin in developing zebrafish that resemble O(2)-chemoreceptive gill NECs. Skin NECs were identified by serotonin immunolabelling and were distributed over the entire skin surface. These cells contained synaptic vesicles and were associated with nerve fibres. Skin NECs were first evident in embryos 24-26 h post-fertilisation (h.p.f.), and embryos developed a behavioural response to hypoxia between 24 and 48 h.p.f. The total number of NECs declined with age from approximately 300 cells per larva at 3 days post-fertilisation (d.p.f.) to ~120 cells at 7 d.p.f., and were rarely observed in adults. Acclimation to hypoxia (30 mmHg) or hyperoxia (300 mmHg) resulted in delayed or accelerated development, respectively, of peak resting ventilatory frequency and produced changes in the ventilatory response to hypoxia. In hypoxia-acclimated larvae, the temporal pattern of skin NECs was altered such that the number of cells did not decrease with age. By contrast, hyperoxia produced a more rapid decline in NEC number. The neurotoxin 6-hydroxydopamine degraded catecholaminergic nerve terminals that made contact with skin NECs and eliminated the hyperventilatory response to hypoxia. These results indicate that skin NECs are sensitive to changes in O(2) and suggest that they may play a role in initiating responses to hypoxia in developing zebrafish.