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The brain uses a specialized system to transport cerebrospinal fluid (CSF), consisting of interconnected ventricles lined by motile ciliated ependymal cells. These cells act jointly with CSF secretion and cardiac pressure gradients to regulate CSF dynamics. To date, the link between cilia-mediated CSF flow and brain function is poorly understood. Using zebrafish larvae as a model system, we identify that loss of ciliary motility does not alter progenitor proliferation, brain morphology, or spontaneous neural activity despite leading to an enlarged telencephalic ventricle. We observe altered neuronal responses to photic stimulations in the optic tectum and hindbrain and brain asymmetry defects in the habenula. Finally, we investigate astroglia since they contact CSF and regulate neuronal activity. Our analyses reveal a reduction in astroglial calcium signals during both spontaneous and light-evoked activity. Our findings highlight a role of motile cilia in regulating brain physiology through the modulation of neural and astroglial networks. [Display omitted] • Smh mutant zebrafish with paralyzed cilia show no major brain malformations • Motile cilia defects lead to an enlarged telencephalic ventricle at larval stages • Altered light-induced neuronal responses in smh mutants • Reduced spontaneous and light-driven glial activity D'Gama et al. study the function of motile cilia in brain development and function. They reveal that cilia paralysis does not affect brain morphology and progenitor proliferation, despite leading to an enlarged telencephalic ventricle. They find that motile cilia regulate sensory-driven neuronal and glial activity. [ABSTRACT FROM AUTHOR]

Bitterlings are carp‐like teleost fish (Cypriniformes: Acheilanathidae) known for their specialized brood parasitic lifestyle. Bitterling embryos, in fact, develop inside the gill chamber of their freshwater mussel hosts. However, little is known about how their parasitic lifestyle affects brain development in comparison to nonparasitic species. Here, we document the development of the brain of the rosy bitterling, Rhodeus ocellatus, at four embryonic stages of 165, 185, 210, 235 hours postfertilization (hpf) using micro‐computed tomography (microCT). Focusing on developmental regionalization and brain ventricular organization, we relate the development of the brain divisions to those described for zebrafish using the prosomeric model as a reference paradigm. Segmentation and three‐dimensional visualization of the ventricular system allowed us to identify changes in the longitudinal brain axis as a result of cephalic flexure during development. The results show that during early embryonic and larval development, histological differentiation, tissue boundaries, periventricular proliferation zones, and ventricular spaces are all detectable by microCT. The results of this study visualized with differential CT profiles are broadly consistent with comparable histological studies, and with the genoarchitecture of teleosts like the zebrafish. Compared to the zebrafish, our study identifies distinct developmental heterochronies in the rosy bitterling, such as a precocious development of the inferior lobe. [ABSTRACT FROM AUTHOR]

Multiciliated ependymal cells and adult neural stem cells are components of the adult neurogenic niche, essential for brain homeostasis. These cells share a common glial cell lineage regulated by the Geminin family members Geminin and GemC1/Mcidas. Ependymal precursors require GemC1/Mcidas expression to massively amplify centrioles and become multiciliated cells. Here, we show that GemC1-dependent differentiation is initiated in actively cycling radial glial cells, in which a DNA damage response, including DNA replication-associated damage and dysfunctional telomeres, is induced, without affecting cell survival. Genotoxic stress is not sufficient by itself to induce ependymal cell differentiation, although the absence of p53 or p21 in progenitors hinders differentiation by maintaining cell division. Activation of the p53-p21 pathway downstream of GemC1 leads to cell-cycle slowdown/arrest, which permits timely onset of ependymal cell differentiation in progenitor cells. [Display omitted] • GemC1 induces ependymal differentiation in cycling progenitors • GemC1 induces DNA damage and p53-p21-p73 expression in ependymal progenitors • p53 and p21 regulate the timing of ependymal cell differentiation • Telomerase hinders centriole amplification and favors a B1 astrocytic fate Ortiz-Álvarez et al. investigate the early steps of multiciliated ependymal cell development using a gain-of-function approach of Geminin family gene members. They report that DNA damage response and p53/p21 activation are involved in the early steps of ependymal cell differentiation immediately downstream of GemC1 in cycling progenitor cells. [ABSTRACT FROM AUTHOR]

The brain ventricular system (BVS) consists of brain ventricles and channels filled with cerebrospinal fluid (CSF). Disturbance of CSF flow has been linked to scoliosis and neurodegenerative diseases, including hydrocephalus. This could be due to defects of CSF production by the choroid plexus or impaired CSF movement over the ependyma dependent on motile cilia. Most vertebrates have horizontal body posture. They retain additional evolutionary innovations assisting CSF flow, such as the Reissner fiber. The causes of hydrocephalus have been studied using animal models including rodents (mice, rats, hamsters) and zebrafish. However, the horizontal body posture reduces the effect of gravity on CSF flow, which limits the use of mammalian models for scoliosis. In contrast, fish swim against the current and experience a forward-to-backward mechanical force akin to that caused by gravity in humans. This explains the increased popularity of the zebrafish model for studies of scoliosis. "Slit-ventricle" syndrome is another side of the spectrum of BVS anomalies. It develops because of insufficient inflation of the BVS. Recent advances in zebrafish functional genetics have revealed genes that could regulate the development of the BVS and CSF circulation. This review will describe the BVS of zebrafish, a typical teleost, and vertebrates in general, in comparative perspective. It will illustrate the usefulness of the zebrafish model for developmental studies of the choroid plexus (CP), CSF flow and the BVS., (© 2022 The Authors. Clinical Anatomy published by Wiley Periodicals LLC on behalf of American Association of Clinical Anatomists and British Association of Clinical Anatomists.)