Intraspinal serotonergic neurons consist of two, temporally distinct populations in developing zebrafish

Jacob E. Montgomery, Timothy D. Wiggin, Luis M. Rivera-Perez, Christina Lillesaar, Mark A. Masino

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Zebrafish intraspinal serotonergic neuron (ISN) morphology and distribution have been examined in detail at different ages; however, some aspects of the development of these cells remain unclear. Although antibodies to serotonin (5-HT) have detected ISNs in the ventral spinal cord of embryos, larvae, and adults, the only tryptophan hydroxylase (tph) transcript that has been described in the spinal cord is tph1a. Paradoxically, spinal tph1a is only expressed transiently in embryos, which brings the source of 5-HT in the ISNs of larvae and adults into question. Because the pet1 and tph2 promoters drive transgene expression in the spinal cord, we hypothesized that tph2 is expressed in spinal cords of zebrafish larvae. We confirmed this hypothesis through in situ hybridization. Next, we used 5-HT antibody labeling and transgenic markers of tph2-expressing neurons to identify a transient population of ISNs in embryos that was distinct from ISNs that appeared later in development. The existence of separate ISN populations may not have been recognized previously due to their shared location in the ventral spinal cord. Finally, we used transgenic markers and immunohistochemical labeling to identify the transient ISN population as GABAergic Kolmer-Agduhr double-prime (KA″) neurons. Altogether, this study revealed a novel developmental paradigm in which KA″ neurons are transiently serotonergic before the appearance of a stable population of tph2-expressing ISNs.

Original languageEnglish (US)
Pages (from-to)673-687
Number of pages15
JournalDevelopmental Neurobiology
Issue number6
StatePublished - Jun 1 2016

Bibliographical note

Funding Information:
Contract grant sponsor: National Institutes of Health (http://; contract grant numbers: R01 NS065054 (to M.A.M.), F31 NS083110 (to T.D.W.), R25 GM096955 (to Dr. Edu B. Suarez Martinez), and R25 NS083059 (to Dr. Robert Meisel). Contract grant sponsor: University of Minnesota Bob Allison Ataxia Research Center (BAARC) (to J.E.M.). Contract grant sponsors: Program Chancengleichheit für Frauen in Forschung und Lehre from the Bayerische Staatsregierung and Julius-Maximilians-Universität Würzburg (to C.L.).

Publisher Copyright:
© 2015 Wiley Periodicals, Inc.


  • Kolmer-Agduhr
  • Pet1
  • Serotonin
  • Spinal cord
  • Tryptophan hydroxylase


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