Diversity and Function of Motile Ciliated Cell Types within Ependymal Lineages of the Zebrafish Brain

Abstract

Motile cilia defects impair cerebrospinal fluid (CSF) flow, and can cause brain and spine disorders. To date, the development of ciliated cells, their impact on CSF flow and their function in brain and axial morphogenesis are not fully understood. Here, we have characterized motile ciliated cells within the zebrafish brain ventricles. We show that the ventricular surface undergoes significant restructuring through development, involving a transition from mono- to multiciliated cells (MCCs) driven by gmnc. MCCs are translationally polarized, co-exist with monociliated cells and generate directional flow patterns. Moreover, these ciliated cells have different developmental origins, and are genetically heterogenous with respect to expression of the Foxj1 family of ciliary master regulators. Finally, we show that cilia loss from specific brain regions or global perturbation of multiciliation does not affect overall brain or spine morphogenesis, but results in enlarged ventricles. Our findings establish that motile ciliated cells are generated by complementary and sequential transcriptional programs to support ventricular development.

Local synchronization of cilia and tissue-scale cilia alignment are sufficient for global metachronal waves

“…Multiciliated epithelia come in many different configurations. They can be sparsely covered with islands of multiciliated cells intermingled with other cell types (10,14,(66)(67)(68), or densely populated with multiciliated cells only (69,70). In this study, we observed that the ciliated epithelium in the developing zebrafish nose falls in the second category, where ciliated cells are densely packed.…”

Biomechanical control of meiotic chromosomal bouquet and germ cell morphogenesis by the zygotene cilium

“…2) Live time-lapse imaging of cilia during chromosomal rotations did not reveal clear beating movement, which is a characteristic of motile cilia (Movie S10-11). 3) Transgenic reporter lines of motile ciliary master transcriptional regulators of the Foxj1 family, [ Tg(foxj1a:GFP) and Tg (foxj1b:GFP) ] ( 72, 73 ), showed no or very weak expression in prophase oocytes within germline cysts where the zygotene cilium forms (Fig. S9).…”

“…Fish lines used in this research are: TU wild type, cep290 fh297 ( 46 ), kif7 i271 ( 53 ), cc2d2a w38 ( 57 ) , tp53 M214K ( 114 ) , Tg(β−act:Arl13b-GFP) ( 115 ), Tg(h2a:H2A-GFP) ( 116 ), Tg(β−act:Cetn2-GFP ( 117 ), Tg(foxj1a:GFP) ( 72, 118 ) , Tg (foxj1b:GFP) ( 72, 118 ), Tg(β−act: mCherry-Cep55l), armc9 zh505 ( 81 ). The Tg(β−act: mCherry-Cep55l) line was generated using the tol2 system.…”

Sustained glymphatic transport and impaired drainage to the nasal cavity observed in multiciliated cell ciliopathies with hydrocephalus

“…The mechanism underlying development of communicating hydrocephalus in ciliopathy is still poorly understood. However, an increasing number of reports in mice, Xenopus and zebrafish have shown that the MCC (ependymal cells) lining the cerebral ventricles are important for: (i) CSF 'near wall' circulation [19,20,22], (ii) transport of nutrients and (iii) secretion of neuropeptides important for directional neural stem cell (NSC) migration (reviewed in Spassky and Meunier, 2017 [69]). Furthermore, genetic studies in humans with hydrocephalus and ciliopathy mouse models have uncovered defective neural stem cell proliferation including impaired cortical neurogenesis [60][61][62]70].…”

“…Another contributor to CSF movement within the CNS involves the motile multi-ciliated cells (MCCs) lining the cerebral ventricles [18,19]. Ex situ studies using organotypic cerebral ventricle explant cultures from rodents and pigs [19], as well as in vivo experiments in Xenopus [20,21] and zebrafish [22], have revealed intricate dynamic patterns of CSF flow through the ventricles orchestrated by the MCCs. However, the role of MCCs in CSF transport and CNS fluid regulation is incompletely understood [23].…”