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Serotonin has a pivotal function regulating development, growth, reproduction and behavior in animals. In this paper, we studied the deregulatory effects of the deprivation of serotonin in  Daphnia magna  TRH CRISPR-Cas9 mutants. Bi-allelic  in-del  THR mutants and, to a lesser extent, mono-allelic ones grew less, reproduced later, and produced smaller clutches than wild type clones. Transcriptomic and functional gene analyses showed a down-regulation of growth/molting and energy metabolism signaling pathways in TRH mutants, while revealing marked differences between mono- and bi-allelic clones. Bi-allelic mutants, lacking serotonin, presented the serotonergic synapse and arachidonic acid metabolic pathways down-regulated while the tryptophan to kynurenine was upregulated, thus indicating a cross-talk between the serotonergic and arachidonic acid metabolic pathways. Finally, the effects on the insulin growth factor-mediated signaling pathway were marginal. These changes in functional and metabolic pathways are consistent with previously reported effects in  D .  magna  exposed to pharmaceuticals that inhibited arachidonic metabolism or enhanced the levels of serotonin.

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Tryptophan hydroxylase (TRH) loss of function mutations in Daphnia deregulated growth, energetic, serotoninergic and arachidonic acid metabolic signalling pathways