Uncovering inherent cellular plasticity of multiciliated ependyma leading to ventricular wall transformation and hydrocephalus

Khadar Abdi, Chun-Hsiang Lai, Patricia Paez-Gonzalez, Mark Lay, Joon Pyun and Chay T. Kuo ()
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Khadar Abdi: Duke University School of Medicine
Chun-Hsiang Lai: Duke University School of Medicine
Patricia Paez-Gonzalez: Duke University School of Medicine
Mark Lay: Duke University School of Medicine
Joon Pyun: Duke University School of Medicine
Chay T. Kuo: Duke University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract Specialized, differentiated cells often perform unique tasks that require them to maintain a stable phenotype. Multiciliated ependymal cells (ECs) are unique glial cells lining the brain ventricles, important for cerebral spinal fluid circulation. While functional ECs are needed to prevent hydrocephalus, they have also been reported to generate new neurons: whether ECs represent a stable cellular population remains unclear. Via a chemical screen we found that mature ECs are inherently plastic, with their multiciliated state needing constant maintenance by the Foxj1 transcription factor, which paradoxically is rapidly turned over by the ubiquitin-proteasome system leading to cellular de-differentiation. Mechanistic analyses revealed a novel NF-κB-independent IKK2 activity stabilizing Foxj1 in mature ECs, and we found that known IKK2 inhibitors including viruses and growth factors robustly induced Foxj1 degradation, EC de-differentiation, and hydrocephalus. Although mature ECs upon de-differentiation can divide and regenerate multiciliated ECs, we did not detect evidence supporting EC’s neurogenic potential.

Date: 2018
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DOI: 10.1038/s41467-018-03812-w

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