Origin of bidirectionality of cerebrospinal fluid flow and impact on long-range transport between brain and spinal cord

Wyart, C.; Thouvenin, O.; Keiser, L.; Cantaut-Belarif, Y.; Carbo Tano, M.; Verweij, F.; Jurisch-Yaksi, N.; Bardet, P.-L.; van Niel, G.; Gallaire, F.

doi:10.1101/627166

bioRxiv · 10.1101/627166

Origin of bidirectionality of cerebrospinal fluid flow and impact on long-range transport between brain and spinal cord

Wyart, C.·Thouvenin, O.·Keiser, L.·Cantaut-Belarif, Y.·Carbo Tano, M.·Verweij, F.·Jurisch-Yaksi, N.·Bardet, P.-L.·van Niel, G.·Gallaire, F.

View original source ↗Export metadata ↓

Abstract

The circulation of cerebrospinal fluid (CSF) plays pivotal roles for body axis formation and brain development. During embryogenesis, CSF is rich in particles and proteins and flows bidirectionally in the central canal. The origins of bidirectional flow and its impact on development are unknown. Experiments combined with modeling and simulations demonstrate that the bidirectionality of CSF flow is generated locally by caudally-polarized motile cilia confined to the ventral wall of the central canal. Such active bidirectional flow of the CSF accelerates the long-range transport of particles propagating rostrally and caudally. In addition, spontaneous muscle contractions increase local CSF flow and consequently enhance long-range transport of extracellular lipidic particles. Focal ablation of the channel connecting brain ventricles to the central canal reduces embryo length, indicating that long-range transport contributes to embryonic growth. Our study also demonstrates that at this early stage, motile cilia ensure the proper formation of the central canal.

Explore related subjects

biophysics Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Wyart, C., Thouvenin, O., Keiser, L., Cantaut-Belarif, Y., Carbo Tano, M., Verweij, F., Jurisch-Yaksi, N., Bardet, P.-L., van Niel, G., Gallaire, F.. 2019-05-07. Origin of bidirectionality of cerebrospinal fluid flow and impact on long-range transport between brain and spinal cord. https://doi.org/10.1101/627166

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Frequency-Dependent Structural Responses of Amyloid-β Fibrils to Terahertz Pulses: A Nonequilibrium Molecular Dynamics Study

The abnormal aggregation of amyloid proteins into fibrils is closely associated with several neurodegenerative diseases, highlighting the importance of developing effective strategies to modulate fibril structural stability. Here, we employed nonequilibrium molecular dynamics(NEMD) simulations to examine the effects of intense terahertz-to-mid-infrared pulses on three amyloid fibrils (2LMP, 2MXU, and 5OQV), focusing on the combined effects of pulse frequency and electric-field strength. Frequency scans from 0.5 to 60 THz in 0.5 THz steps revealed frequency-dependent losses of {beta}-sheet content, with several common response patterns in these fibrils. Comparisons at 2, 23, 33, and 50 THz showed that pulse-induced changes in secondary structure differed from those in high-temperature controls. Hydrogen-bond analysis showed that total hydrogen-bond counts could partially recover even as interchain hydrogen bonds continued to decrease, with distinct responses among representative chain pairs. We therefore propose a two-threshold electric-field framework for fibril disruption: Eth1 describes the onset of structural perturbation, whereas Eth2 indicates persistent structural loss after the pulse. This framework offers a testable approach for characterizing amyloid structural responses to external fields, although the underlying energy-coupling mechanisms, quantitative thresholds, and long-term recovery require further validation. These findings may provide a theoretical basis for exploring external-field-based strategies to modulate protein aggregation.

biophysics↗

bioRxiv2026

Organised streaming of cerebrospinal fluid in the human third ventricle

Quasi-periodic pressure pulses associated with cardiac and respiratory activity generate reciprocating cerebrospinal fluid (CSF) motion in the human ventricles. Regular waves dominated by the cardiac cycle are overlaid with cycles of low-frequency respiratory waves, the latter to become stronger in forced breathing or even dominated by large successive flushes in NREM sleep. The present study investigates how such waves contribute to residual streaming within the human ventricles. Transient CFD simulations were performed in the third ventricle at varying parameters of frequency, stroke volume and wave-form asymmetry. Increasing the aqueduct peak Reynolds-number, either by small stroke volume and high frequency or large stroke volume at low frequency, transfers the flow from a reversible flow pattern to the formation of clear preferential pathways, alternating between the in- and outflow cycle. The resulting permanent streaming flux across the aqueduct relative to the mean oscillatory flow-rate, i.e. the dimensionless streaming ratio SR follows a rational saturation relation, SR [~] ReAq,peak/(C + ReAq,peak), demonstrating that increasing the peak aqueduct Reynolds number yields diminishing returns and bounds the relative contribution of residual inter-ventricular streaming. These findings demonstrate differences in hydrodynamic organisation in the third ventricle and highlight the importance of this organisation for intraventricular fluid exchange.

biophysics↗

bioRxiv2026

Amyloid stability and condensate material properties independently govern the hnRNPA2 condensate to fibril transition

hnRNPA2 is a component of cellular membraneless organelles many of which contain RNA and RNA-binding proteins (RBPs). RBPs frequently contain low-complexity domains (LCDs) that can also assemble into amyloid fibrils. Fibrils isolated from patients with frontotemporal lobar degeneration contain ordered segments of these LCDs and disease-associated mutations can enhance the homotypic interactions that promote aggregation. Although previous studies have largely examined the condensate-to-fibril transition by altering condensate stability, how amyloid structure governs this process remains poorly understood. Here, we show that the hnRNPA2 LCD forms a reproducible fibril fold and by combining structure-guided thermodynamic profiling, peptide design, mutagenesis and in vitro characterization under conditions with (two-phase) and without (one-phase) condensates, we define the molecular determinants of its assembly. We identify an aromatic triad within the fibril core that controls fibril formation kinetics and thermodynamic stability. Mutational analysis further reveals that condensate stability and fibril stability are largely independent. Finally, microrheology linked reduced condensate viscosity to faster fibril formation, supporting a role for condensate material properties in regulating aggregation kinetics. Together, these findings support a model in which the condensate-to-fibril transition is governed by the interplay between a disordered ''fuzzy coat'' and a fibril-forming aromatic triad within hnRNPA2. This work provides a structural framework for understanding how condensates can transition into amyloid assemblies.

biophysics↗