# Structure and function of a novel population of regenerating ependymal cells

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $427,996

## Abstract

PROJECT SUMMARY
The laboratory has identified a novel type of ependymal cell (E2) that has two long cilia anchored by two basal
bodies that are 30-100 fold larger than those in other cells (Mirzadeh et al. 2008, 2017). E2 cells are found in
strategic locations of the ventricular system, next to Neural Stem Cells (NSCs) in the walls of the lateral
ventricle and in regions of the third and fourth ventricle critical to feeding and glucose regulation, circadian
rhythms, consciousness, alertness and sleep (Mirzadeh et al. 2017). Interestingly, E2-like cells have been also
observed in ependymomas, suggesting a link to proliferating progenitors and cancer (Alfaro-Cervelló et al.
2015; Ho, Caccamo, and Garcia 1994). E2 cells' genetic profile, the composition and organization of their
unique cilia and basal bodies, their developmental origin, their regenerative capacity, and their function are not
known. Ependymal (E) cells remain one of the least understood glial cell types in the brain, yet these cells are
involved in functions that are essential for proper brain function. Multiciliated ependymal (E1) cells, through the
coordinated beating of their ~50 motile cilia, contribute to cerebrospinal fluid (CSF) flow, and are required to
prevent hydrocephalus (Jiménez et al. 2014; Ohata and Alvarez-Buylla 2016; Banizs et al. 2005). In the lateral
ventricles, E cells contribute to the regulation of adult neural stem cells (NSCs) and neuronal migration in the
largest germinal zone of the adult brain: the ventricular-subventricular zone (V-SVZ). How E cells sense and
transmit CSF signals to this germinal niche remains unknown. It is unlikely that E2 cells through their two cilia
contribute significantly to CSF flow. Instead, we propose that E2 cilia and basal body could play a key role in
the detection of CSF signals. Their location at the interface between the CSF and important brain regions
strongly suggests they have pivotal, as-yet unidentified, roles in brain function. Surprisingly, preliminary data
indicate that the lateral ventricle E2 cells are relatively short-lived, decrease in number with age, and are
constantly regenerated in adult mice. We propose to: 1) characterize E2 cells and their cilia and basal bodies
using single cell gene expression analysis, electron and ultra-high resolution microscopy; 2) determine the
development and adult population dynamics of E2 cells, and identify the progenitor cells giving rise to new E2
cells in the adult (preliminary evidence suggests that E2 cells are derived from adult NSCs); and 3) investigate
whether E2 cell cilia signaling modulates adult stem cell niche function, using conditional deletion of a key cilia
signaling molecule enriched in E2 cells. This new knowledge will be essential to decipher the function of E2
cells in the adult V-SVZ. In addition, molecular markers and signaling pathways identified in E2 cells could help
understand the cell of origin and growth control of some ependymomas. Given the prese...

## Key facts

- **NIH application ID:** 9863501
- **Project number:** 1R01NS113910-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Arturo Alvarez-Buylla
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $427,996
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9863501

## Citation

> US National Institutes of Health, RePORTER application 9863501, Structure and function of a novel population of regenerating ependymal cells (1R01NS113910-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9863501. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*