Majority of cerebrospinal fluid-contacting neurons in the spinal cord of C57Bl/6N mice is present in ectopic position unlike in other studied experimental mice strains and mammalian species

J Comp Neurol. 2020 Oct 15;528(15):2523-2550. doi: 10.1002/cne.24909. Epub 2020 Apr 9.


Cerebrospinal fluid contacting neurons (CSF-cNs) represent a specific class of neurons located in close vicinity of brain ventricles and central canal. In contrast with knowledge gained from other vertebrate species, we found that vast majority of CSF-cNs in the spinal cord of C57Bl/6N mice is located in ectopic distal ventral position. However, we found that small number of ectopic CSF-cNs is present also in spinal cord of other investigated experimental mice strains (C57Bl/6J, Balb/C) and mammalian species (Wistar rats, New Zealand White rabbits). Similarly, as the proximal populations, ectopic CSF-cNs retain PKD2L1-immunoreactivity and synaptic contacts with other neurons. On the other side, they show rather multipolar morphology lacking thick dendrite contacting central canal lumen. Ectopic CSF-cNs in the spinal cord of C57Bl/6N mice emerge during whole period devoted to production of CSF-cNs and reach their ventral destinations during first postnatal weeks. In order to identify major gene, whose impairment could trigger translocation of CSF-cNs outside the central canal area, we took advantage of close consanguinity of C57Bl/6J substrain with normal CSF-cN distribution and C57Bl/6N substrain with majority of CSF-cNs in ectopic position. Employing in silico analyses, we ranked polymorphisms in C57Bl/6N substrain and selected genes Crb1, Cyfip2, Adamts12, Plk1, and Herpud2 as the most probable candidates, whose product dysfunction might be responsible for the ectopic distribution of CSF-cNs. Furthermore, segregation analysis of F2 progeny of parental C57Bl/6N and Balb/C mice revealed that polymorphic loci of Crb1 and Cyfip2 underlie the ectopic position of CSF-cNs in the spinal cord of C57Bl/6N mice.

Keywords: C57Bl/6N; CSF-cNs; Crb1; Cyfip2; PKD2L1; Polycystin-L; ependyma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebrospinal Fluid / physiology*
  • Choristoma / genetics
  • Choristoma / pathology
  • Female
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neurons / metabolism*
  • Neurons / physiology*
  • Pregnancy
  • Rabbits
  • Rats
  • Rats, Wistar
  • Species Specificity
  • Spinal Cord / physiology*
  • Spinal Cord / ultrastructure*