Comparative analysis of monoaminergic cerebrospinal fluid-contacting cells in Osteichthyes (bony vertebrates)

J Comp Neurol. 2017 Jun 15;525(9):2265-2283. doi: 10.1002/cne.24204. Epub 2017 Mar 29.


Cerebrospinal fluid-contacting (CSF-c) cells containing monoamines such as dopamine (DA) and serotonin (5-HT) occur in the periventricular zones of the hypothalamic region of most vertebrates except for placental mammals. Here we compare the organization of the CSF-c cells in chicken, Xenopus, and zebrafish, by analyzing the expression of synthetic enzymes of DA and 5-HT, respectively, tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), and draw an evolutionary scenario for this cell population. Due to the lack of TH immunoreactivity in this region, the hypothalamic CSF-c cells have been thought to take up DA from the ventricle instead of synthesizing it. We demonstrate that a second TH gene (TH2) is expressed in the CSF-c cells of all the three species, suggesting that these cells do indeed synthetize DA. Furthermore, we found that many CSF-c cells coexpress TH2 and TPH1 and contain both DA and 5-HT, a dual neurotransmitter phenotype hitherto undescribed in the brain of any vertebrate. The similarities of CSF-c cells in chicken, Xenopus, and zebrafish suggest that these characteristics are inherited from the common ancestor of the Osteichthyes. A significant difference between tetrapods and teleosts is that teleosts possess an additional CSF-c cell population around the posterior recess (PR) that has emerged in specific groups of Actinopterygii. Our comparative analysis reveals that the hypothalamus in mammals and teleosts has evolved in a divergent manner: placental mammals have lost the monoaminergic CSF-c cells, while teleosts have increased their relative number.

Keywords: CSF-contacting cells; RRID: AB_10000240; RRID: AB_2201528; RRID: AB_221448; RRID: AB_2314334; RRID: AB_2314655; RRID: AB_477522; RRID: AB_87181; RRID: AB_94865; dopamine; evolution; hypothalamus; monoamine; paraventricular organ; serotonin; ventricle.

MeSH terms

  • Animals
  • Biogenic Monoamines / metabolism*
  • Biological Evolution
  • Brain / cytology*
  • Brain / metabolism
  • Cerebrospinal Fluid / physiology*
  • Chick Embryo
  • Chickens
  • ELAV Proteins / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Imaging, Three-Dimensional
  • Male
  • Neurons / classification
  • Neurons / metabolism*
  • RNA, Messenger / metabolism
  • Vertebrates
  • Xenopus
  • Zebrafish
  • Zonula Occludens-1 Protein / metabolism


  • Biogenic Monoamines
  • ELAV Proteins
  • RNA, Messenger
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • Green Fluorescent Proteins