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

Abstract

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.

Evidence for PKD2L1-positive neurons present distant from the central canal in the ventromedial spinal cord and Medulla of the adult mouse

“…A recent study suggested that ventral PKD2L1 + cells might be the result of ectopic distribution that depends on the animal models or strains tested (Tonelli Gombalová et al, 2020). In agreement with our study, the authors reported the presence of distal PKD2L1 expressing neurons in several animal models as well as in the C57Bl6/J (the mouse line used in our study).…”

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pathological dysfunction. Finally, although CSF-cN neurogenesis has been shown to occur only during development they have been shown to retain an incomplete maturity state (Stoeckel et al, 2003;Sabourin et al, 2009;Orts-Del'Immagine et al, 2014 and might be reactivated and take part to plasticity and regenerative processes associated with the ependymal stem cell niche.Most studies focused on ependymal and sub-ependymal PKD2L1 + CSF-cNs (located at less than 50 µm from the CC) however previous observations (Orts-Del'immagine et al, 2012;Djenoune et al, 2014;Orts-Del'Immagine et al, 2014), recently confirmed (Tonelli Gombalová et al, 2020), mentioned the presence of PKD2L1 + cells located more distally from the CC. The developmental origin for these distal PKD2L1 + cells is still unclear but as ependymal cells located along the ventral midline in regions distal from the CC display specific electrophysiological properties of neuronal progenitor (eg.

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“…Most studies focused on ependymal and sub-ependymal PKD2L1 + CSF-cNs (located at less than 50 µm from the CC) however previous observations (Orts-Del'immagine et al, 2012;Djenoune et al, 2014;Orts-Del'Immagine et al, 2014), recently confirmed (Tonelli Gombalová et al, 2020), mentioned the presence of PKD2L1 + cells located more distally from the CC. The developmental origin for these distal PKD2L1 + cells is still unclear but as ependymal cells located along the ventral midline in regions distal from the CC display specific electrophysiological properties of neuronal progenitor (eg.…”

The Neural Stem Cell Properties of PKD2L1+ Cerebrospinal Fluid-Contacting Neurons in vitro

“…These results suggested that CSF-cNs maintain a relatively primitive cell phenotype and show a strong potential as NSCs during in vitro culture. Petracca and Colleagues showed that CSF-cNs were negative for GFAP in animal tissues, a marker both for astrocyte and neural stem cell (Petracca et al, 2016;Tonelli Gombalova et al, 2020). But in our research, GFAP was expressed in primary culture of CSF-cNs and neurospheres formed by CSF-cNs in cell culture.…”

Molecular markers of mechanosensation in glycinergic neurons in the avian lumbosacral spinal cord

“…There is no clear connection between CSF-cNs and the glyt2+ cells reported here. While CSF-cNs can be found ectopically (outside of the ependymal layer surrounding the central canal; [17,6]), they are known to be GABAergic across vertebrates [3]. Further, a recent transcriptome analysis of spinal dynophin-lineage cells found a cluster with characteristics of CSF-cNs but comparatively low expression of glyt2 transcript (SLC6A5; Fig.…”