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    Review of 'Serotonin is required for pharyngeal arch morphogenesis in zebrafish'

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    Serotonin is required for pharyngeal arch morphogenesis in zebrafishCrossref
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    Serotonin is required for pharyngeal arch morphogenesis in zebrafish

    Serotonin (5-HT) is not only a neurotransmitter but also a mediator of developmental processes in vertebrates. In this study, we analyzed the importance of 5-HT during zebrafish development. The expression patterns of three zebrafish tryptophan hydroxylase isoforms (Tph1A, Tph1B, Tph2), the rate-limiting enzymes in 5-HT synthesis, were analyzed and compared to the appearance and distribution of 5-HT. 5-HT was found in the raphe nuclei correlating with tph2 expression and in the pineal gland correlating with tph1a and tph2 expression. tph2 deficient fish generated with antisense morpholino oligonucleotides exhibited morphogenesis defects during pharyngeal arch development. The correct specification of neural crest cells was not affected in tph2 morphants as shown by the expression of early markers, but the survival and differentiation of pharyngeal arch progenitor cells were impaired. An organizing role of 5-HT in pharyngeal arch morphogenesis was suggested by a highly regular pattern of 5-HT positive cells in this tissue. Moreover, the 5-HT2B receptor was expressed in the pharyngeal arches and its pharmacological inhibition also induced defects in pharyngeal arch morphogenesis. These results support an important role of Tph2-derived serotonin as a morphogenetic factor in the development of neural crest derived tissues.
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      Serotonin is known to play a role as a morphogen in early embryonic development. In rodents, the role of serotonin in somatosensory cortex patterning is well documented. The current study further extends our understanding of serotonin in the pharyngeal arch morphogenesis in zebrafish, and more generally, neural crest specification and differentiation. This study is carefully designed. The article is well presented and discussed. I only have one comment for the authors:
      Since ritanserin is a general 5-HT2 receptor antagonist (it has a similar binding affinity for 2A, 2B and 2C), therefore, it would be more cautious to draw a conclusion that the pharyngeal arch morphogenesis is mediated by 5-HT2B receptor.

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