The role of motile cilia in the development and physiology of the nervous system

Abstract

Motile cilia are miniature, whip-like organelles whose beating generates a directional fluid flow. The flow generated by ciliated epithelia is a subject of great interest, as defective ciliary motility results in severe human diseases called motile ciliopathies. Despite the abundance of motile cilia in diverse organs including the nervous system, their role in organ development and homeostasis remains poorly understood. Recently, much progress has been made regarding the identity of motile ciliated cells and the role of motile-cilia-mediated flow in the development and physiology of the nervous system. In this review, we will discuss these recent advances from sensory organs, specifically the nose and the ear, to the spinal cord and brain ventricles. This article is part of the Theo Murphy meeting issue 'Unity and diversity of cilia in locomotion and transport'.

Keywords: Foxj1; cerebrospinal fluid; cilia; ependymal cell; nervous system; olfaction.

Figure 1.

Schematic depiction of sensory and ventricular systems across vertebrates. (a–d) Olfactory organs (green), inner ears (orange), ventricular systems (blue) and central nervous systems (pink) in zebrafish (a), frog (b), mouse (c) and human (d) are shown. Sensory regions in olfactory organs are coloured dark green, while non-sensory regions are light green. Three-dimensional renderings of brain ventricular systems of (a′) a 2-day old zebrafish [25], (a″) a three-month-old zebrafish [26], (b′) a stage 45 Xenopus tropicalis [27], (c′) an average adult mouse [28] and (d′) an adult human [29] are shown. TV, telencephalic; DV, diencephalic ventricle; TeV, tectal ventricle; RV, rhombencephalic ventricle; LV, lateral ventricle; 3V, 3rd ventricle; MV, mesencephalic ventricle; 4V, 4th ventricle.

Figure 2.

Schematic depiction of various cavities of the nervous system lined with motile cilia. (a) The olfactory organ of a zebrafish larva is composed of multiciliated cells (MCC) located at the outer rim of the nasal cavity. MCC bear multiple motile cilia (magenta), which generate a directional fluid flow of water. Ciliated OSNs (green), which bear multiple primary cilia (black) and microvilli OSN (grey) are located at the bottom of the nasal cavity. (b,b′) The otic vesicle of a zebrafish embryo at 18–24 hpf contains hair cells (green), or tether cells, that bear primary cilia capable of tethering the otolith (blue). Next to hair cells, there are motile cilia on supporting cells that generate a rotational flow near the otolith. (c) The central canal of the spinal cord is composed of cerebrospinal fluid-contacting neurons (CSF-cNs; green), which bear a microvilli tuft and a motile cilium in zebrafish. ECC (grey), also known as ERG in zebrafish, are located on the floor plate or the dorsal wall of the central canal and bear a cilium. Note that there are more motile cilia in the ventral part of the central canal than the dorsal plane at early developmental stage, and that the CSF flow is bidirectional. (d) The brain ventricular system of the zebrafish larva is decorated by motile cilia (magenta) at very specific locations along the midline. Motile-cilia-mediated flow is complex and compartmentalized to individual ventricles. (d′) Sagittal view of the inset in (d) showing that cells bear a single cilium oriented anteriorly in the same direction as fluid flow. (d″) Transverse view shows that motile cilia are located in the ventral and dorsal wall of the diencephalic-tectal ventricle. Elsewhere, radial glia (RG, green) project their primary cilium into the CSF-filled cavity. (e) ECs, which bear motile cilia, are located along the medial and lateral wall of the mouse lateral ventricle. (e′) Transverse section through the inset in (e) reveals that NSCs of the SVZ are located directly under the ependyma layer made of multiciliated E1 cells and bi-ciliated E2 cells. NSCs also known as B cells (green) project their primary cilium towards the CSF-filled ventricle in addition to contacting the blood vessel (blue), while transient amplifying cells (C cells, grey) and migrating neuroblasts (A cells, grey) lose their direct interaction with the CSF. En face representation shows the pinwheel structure composed of E1 and B cells. Note the translational polarity of the motile cilia of E1 cells. A, anterior; P, posterior; L, left; R, right; D, dorsal; V, ventral; M, medial; Lat, lateral. Motile cilia are in magenta, primary cilia are in black.