Abstract

Defects in cerebrospinal fluid (CSF) flow may contribute to idiopathic scoliosis. However, the mechanisms underlying detection of CSF flow in the central canal of the spinal cord are unknown. Here we demonstrate that CSF flows bidirectionally along the antero-posterior axis in the central canal of zebrafish embryos. In the cfap298tm304 mutant, reduction of cilia motility slows transport posteriorly down the central canal and abolishes spontaneous activity of CSF-contacting neurons (CSF-cNs). Loss of the sensory Pkd2l1 channel nearly abolishes CSF-cN calcium activity and single channel opening. Recording from isolated CSF-cNs in vitro, we show that CSF-cNs are mechanosensory and require Pkd2l1 to respond to pressure. Additionally, adult pkd2l1 mutant zebrafish develop an exaggerated spine curvature, reminiscent of kyphosis in humans. These results indicate that CSF-cNs are mechanosensory cells whose Pkd2l1-driven spontaneous activity reflects CSF flow in vivo. Furthermore, Pkd2l1 in CSF-cNs contributes to maintenance of natural curvature of the spine.

Details

Title
Pkd2l1 is required for mechanoception in cerebrospinal fluid-contacting neurons and maintenance of spine curvature
Author
Sternberg, Jenna R 1   VIAFID ORCID Logo  ; Prendergast, Andrew E 2 ; Brosse, Lucie 3 ; Cantaut-Belarif, Yasmine 2 ; Thouvenin, Olivier 4   VIAFID ORCID Logo  ; Adeline Orts-Del’Immagine 2 ; Castillo, Laura 3 ; Djenoune, Lydia 5 ; Kurisu, Shusaku 6 ; McDearmid, Jonathan R 7 ; Pierre-Luc Bardet 2 ; Boccara, Claude 8 ; Okamoto, Hitoshi 9 ; Delmas, Patrick 3 ; Wyart, Claire 2 

1  Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, AP-HP, Institut du Cerveau et de la Moelle épinière (ICM) - Hôpital Pitié-Salpêtrière, Paris, France; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA 
2  Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, AP-HP, Institut du Cerveau et de la Moelle épinière (ICM) - Hôpital Pitié-Salpêtrière, Paris, France 
3  Aix Marseille Université, CNRS, Laboratoire de Neurosciences Cognitives-UMR7291, Marseille, France 
4  Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, AP-HP, Institut du Cerveau et de la Moelle épinière (ICM) - Hôpital Pitié-Salpêtrière, Paris, France; PSL Research University, Institut Langevin, ESPCI Paris, Paris, France 
5  Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, AP-HP, Institut du Cerveau et de la Moelle épinière (ICM) - Hôpital Pitié-Salpêtrière, Paris, France; Department of Medicine, Nephrology Division and Harvard Medical School, Department of Genetics, Massachusetts General Hospital, Charlestown, MA 02115, USA 
6  Riken Brain Science Institute, Wako, Saitama 351-0198, Japan; Department of Cell Biology, Tokushima University Graduate School of Medical Science, Tokushima 770-8503, Japan 
7  Department of Neuroscience, Psychology & Behaviour, College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, UK 
8  PSL Research University, Institut Langevin, ESPCI Paris, Paris, France 
9  Riken Brain Science Institute, Wako, Saitama 351-0198, Japan 
Pages
1-10
Publication year
2018
Publication date
Sep 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-06225-x
ProQuest document ID
2108829259
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.