The dual developmental origin of spinal cerebrospinal fluid-contacting neurons gives rise to distinct functional subtypes

Lydia Djenoune,Feng B Quan,Dominique Langui,Filippo Del Bene,Hugo Marnas,Andrew Prendergast,Laura Desban,Jean-Paul Rio,Thomas O Auer,Johanna Gomez,Claire Wyart,Pierre-Luc Bardet,Jenna R Sternberg

doi:10.1038/s41598-017-00350-1

Abstract

Chemical and mechanical cues from the cerebrospinal fluid (CSF) can affect the development and function of the central nervous system (CNS). How such cues are detected and relayed to the CNS remains elusive. Cerebrospinal fluid-contacting neurons (CSF-cNs) situated at the interface between the CSF and the CNS are ideally located to convey such information to local networks. In the spinal cord, these GABAergic neurons expressing the PKD2L1 channel extend an apical extension into the CSF and an ascending axon in the spinal cord. In zebrafish and mouse spinal CSF-cNs originate from two distinct progenitor domains characterized by distinct cascades of transcription factors. Here we ask whether these neurons with different developmental origins differentiate into cells types with different functional properties. We show in zebrafish larva that the expression of specific markers, the morphology of the apical extension and axonal projections, as well as the neuronal targets contacted by CSF-cN axons, distinguish the two CSF-cN subtypes. Altogether our study demonstrates that the developmental origins of spinal CSF-cNs give rise to two distinct functional populations of sensory neurons. This work opens novel avenues to understand how these subtypes may carry distinct functions related to development of the spinal cord, locomotion and posture.

Highlights

Chemical and mechanical cues from the cerebrospinal fluid (CSF) can affect the development and function of the central nervous system (CNS)
Spinal Cerebrospinal fluid-contacting neurons (CSF-cNs) were previously shown to originate from distinct progenitor domains characterized by distinct pools of transcription factors in the embryo[26, 29, 30]
We demonstrate that these two domains give rise to two cell types of CSF-cNs with probably distinct functional properties at the larval stages (Supplemental Fig. 8)

Summary

Introduction

Chemical and mechanical cues from the cerebrospinal fluid (CSF) can affect the development and function of the central nervous system (CNS). Multiple studies indicate that the CSF conveys signals affecting the development and output functions of the CNS, such as feeding, sleep, and locomotion[2,3,4,5,6] These observations suggest that chemical or mechanical cues from the CSF may act on neurons in the brain and spinal cord. There is evidence that spinal CSF-cNs do not constitute a homogeneous population of neurons These cells originate from distinct progenitor domains and are specified differentially by several cascades of transcription factors[26, 29,30,31,32]. Our results show that spinal CSF-cNs constitute two distinct functional cell types that differ in apical and axonal morphology, neuronal targets within the spinal cord as well as in the transient expression of secreted compounds

Methods

Results

Conclusion