- Hair-like motile cilia maintain the flow of cerebrospinal fluid (CSF) within the brain ventricles by their beating action
- Circulating CSF provides nutrients to developing nerve cells
- This helps in the development of the brain and maintaining its function
Cilia are miniature, hair-like protrusions that emanate from many types of cells throughout the body, including the brain. The inner walls of the brain's cavities, called ventricles, are lined with these tiny cilia. These cilia help in the flow of cerebrospinal fluid (CSF) within the ventricles of the brain. The beating of these motile cilia is crucial, as patients with defective cilia can develop serious disease conditions such as hydrocephalus and scoliosis.
Scientists from the Yaksi group at the Kavli Institute for Systems Neuroscience / Center for Neural Computation, at the Norwegian University of Science and Technology (NTNU), Trondheim, Norway, have shown that cilia are essential for the normal development of the brain. The study has been published in Current Biology, a Cell Press publication.
Function of CSF Circulation in the BrainThe human brain has four fluid-filled ventricles, which are connected with each other. The ventricles are filled with CSF, which is produced within these brain cavities. Within the brain, special types of cells called ependymal cells extend their cilia into the ventricles and help in CSF flow. This causes the CSF to be in a state of constant motion within the ventricles, which varies with the movement of the body. The function of CSF is still debatable.
"The cerebrospinal fluid flow also contributes to transmitting molecular signals across the brain," says Emre Yaksi, Professor and the Head of the Yaksi Group at the Kavli Institute.
The research team used zebrafish as a vertebrate model organism to study these phenomena.
Why are Zebrafish Useful for This Type of Study?Zebrafish are the ideal vertebrate model organisms for this type of study, as it can't be done in humans due to ethical and practical reasons. Zebrafish, being vertebrates, just like humans, can help to study how the brain develops and functions. Zebrafish larvae were used for the study, which are particularly useful because they are transparent and therefore can be studied in minute detail - even each individual cell and cilia. Moreover, the investigations can be carried out without the need for any intervention and without harming the fish in any way.
Role of Ciliary Motion in Regulating CSF FlowCilia may be motile or non-motile, which are also called primary cilia. In the present study, the Yaksi group focused their research on motile cilia. These cilia beat in a coordinated manner that generates a directional fluid flow, which is essential for various biological functions, including respiration and reproduction. For example, during respiration, the beating of cilia pushes out any mucus or air pollutants that accumulate within the respiratory tract. During reproduction, the cilia move the egg along the fallopian tube into the uterus by their coordinated beating action.
The Yaksi group found that unlike the cilia of the respiratory or reproductive tracts, the cilia present within the ventricles in the brain of developing zebrafish larvae exhibit a propeller-like motion, similar to the tail of a sperm.
The researchers found that different populations of cells with motile cilia were distributed in distinct regions within the ventricles. The beating of these cilia generated a directional CSF flow, which was largely confined within individual ventricular cavities. There was only a small fraction of CSF exchange between the ventricles, in spite of the pulsatile motion generated by the heartbeats.
This compartmentalization of CSF was disrupted by the movement of the body, which indicates that multiple physiological processes impact the flow of CSF within the ventricles. However, compartmentalization is needed to keep the ducts between the ventricles open. Importantly, CSF flow within a ventricle or between ventricles depends on whether the body is stationary or moving.
"We found surprisingly little exchange of fluid between the ventricles as long as the fish were at rest, even though the heartbeat pulsations caused some flow between them," says Ph.D. candidate Emilie Willoch Olstad, who is the first author of the article in Current Biology.
Role of Ciliary Motion in Nerve Cell DevelopmentIt has been suggested that the beating of cilia could play an indirect role in nerve cell development by regulating the flow of CSF in the brain. In fact, recent studies have found that the motion of CSF could play a role in brain development and function.
It has been found that nerve cells are derived from the inner lining of the ventricles and migrate to other regions of the brain for further development and differentiation. These processes require the uptake of nutrients that are distributed within the ventricles by the circulating CSF. It has been observed that in zebrafish, the development of neurons (neurogenesis), not only occurs in the developing brain of the larval stage, but also in adult fish. Importantly, recent studies have shown that neurogenesis that occurs in adult zebrafish, also occur in humans.
Future PlansThe research team plans to explore the possibility of altering the brain function of zebrafish by manipulating the motility of cilia. This would involve studying the fluctuations in neural activity or circadian rhythms in zebrafish, as a result of changes in CSF flow due to perturbations in cilia motility.
- Ciliary beating compartmentalizes cerebrospinal fluid flow in the brain and regulates ventricular development - (https://www.cell.com/current-biology/fulltext/S0960-9822(18)31589-6)