The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord

Abstract

Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. However, how the timing of differentiation contributes to neuronal diversity in the developing spinal cord is still a pending question. In this study, we show that cerebrospinal fluid-contacting neurons (CSF-cNs), an anatomically discrete cell type of the ependymal area, originate from surprisingly late neurogenic events in the ventral spinal cord. CSF-cNs are identified by the expression of the transcription factors Gata2 and Gata3, and the ionic channels Pkd2l1 and Pkd1l2. Contrasting with Gata2/3 + V2b interneurons, differentiation of CSF-cNs is independent of Foxn4 and takes place during advanced developmental stages previously assumed to be exclusively gliogenic. CSF-cNs are produced from two distinct dorsoventral regions of the mouse spinal cord. Most CSF-cNs derive from progenitors circumscribed to the late-p2 and the oligodendrogenic ( pOL) domains, whereas a second subset of CSF-cNs arises from cells bordering the floor plate. The development of these two subgroups of CSF-cNs is differentially controlled by Pax6, they adopt separate locations around the postnatal central canal and they display electrophysiological differences. Our results highlight that spatiotemporal mechanisms are instrumental in creating neural cell diversity in the ventral spinal cord to produce distinct classes of interneurons, motoneurons, CSF-cNs, glial cells and ependymal cells.

Transcriptional Regulation of Notch1 Expression by Nkx6.1 in Neural Stem/Progenitor Cells during Ventral Spinal Cord Development

“…Adult ependymal cells are originated from the Nkx6.1+/Gata2+/Gata3+ ventral spinal progenitors and maintain Nkx6.1 expression4041. In consistent with these studies, we observed that CR2-GFP+ ependymal cells of adult spinal cord were positive for Nkx6.1 and Notch1 (Fig.…”

Neural stem/progenitor cells are activated during tail regeneration in the leopard gecko (Eublepharis macularius)

“…A small number of ELCs within the regenerating spinal cord also express TUJ1. Of note, these TUJ1+ cells demonstrate a staining pattern similar to that observed in the developing mouse spinal cord (Petracca et al, ) and suggest that some ELCs of the regenerate tail demonstrate neuronal‐like properties. Taken together, our SOX9 and TUJ1 data strongly support the idea that regenerate spinal cord ELCs are a heterogeneous population.…”

“…To confirm the absence of neurons in regenerated tails, we immunostained with the neuronal markers NeuN and HuC/D (Figure ). Whereas NeuN is considered to be a marker of mature neurons within the spinal cord, HuC/D is expressed by mature and immature neurons, as well as some neuronal‐like cell types (e.g., cerebrospinal fluid contacting (CSF‐c) cells; (Marichal, García, Radmilovich, Trujillo‐Cenóz, & Russo, ; Petracca et al, ). As expected, NeuN immunopositive (+) cells were present throughout the grey matter of the original spinal cord (Figure a, b), but entirely absent from the fully regenerated spinal cord (Figure c, d).…”

Whole-organism cellular gene-expression atlas reveals conserved cell types in the ventral nerve cord of Platynereis dumerilii

“…In addition, because phenotypic similarities-and thus, similarities in gene expression-can also arise by convergent or concerted evolution (2), validation of the proposed homologies will require more extensive molecular characterization, including the functional validation of transcription factor involvement in cell-type specification and, ideally, single-cell transcriptomics for an unbiased account of all cellular modules used by each type (35). The proposed ancient nature of a neuron-type clade specified by a Gata1/2/3-Tal CoRC finds support by recent studies showing that the same transcription factors are also expressed in Kolmer-Agduhr neurons in fish (23) and in the corresponding central spinal fluid-expressing neurons in mouse (36). KolmerAgduhr neurons are hair cell-like sensory neurons that contact the central canal and send out ipsilateral ascending axons (37).…”