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Epithelial organization of the adult neural stem cell niche

  • Author(s): Mirzadeh, Zaman
  • Advisor(s): Alvarez-Buylla, Arturo
  • et al.
Abstract

The adult mammalian brain, for all of its complexity, develops from a single cell layered epithelium of neural stem cells. These stem cells are retained in the epithelium lining the embryonic brain ventricles throughout development. Postnatally however, this germinal epithelium is replaced by postmitotic multiciliated ependymal cells. Neural stem cells are retained in the adult brain, but they are displaced from the ventricular epithelium and it is generally thought that they do not maintain epithelial properties. In this dissertation, I challenge this notion. Using a wholemount imaging technique that allows en-face examination of the ventricular walls, I show that the adult brain lateral ventricle is lined by a mixed neuroepithelium of multiciliated ependymal cells and adult neural stem cells (type B cells). Type B cells have very small ventricle-contacting apical surfaces observed only in neurogenic niches of the adult ventricular system. At their apical surface, B cells extend a primary cilium into the ventricle and are surrounded by ependymal cells, forming pinwheel structures that appear as repeating units across the neuroepithelium. Type B cells also contain a previously unidentified long basal process ending on blood vessels. These adult neural stem cells therefore display apical-basal polarity. En-face analysis of the ventricular walls also reveals a third cell type in the ventricular epithelium, which I call E2 cells. These cells are bi-ciliated with a novel basal body structure containing elaborate lateral extensions. Finally, in addition to apical-basal polarity, the adult ventricular epithelium has planar polarity evident in the polarized beating of ependymal cilia, which propels cerebrospinal fluid through the ventricular system and is essential to normal brain function. I describe two reliable anatomical correlates to ependymal planar polarity: the rotational orientation of basal bodies and their translational position on the apical surface of ependymal cells. I show that this planar polarity does not require ependymal cilia. Altogether, this work reveals the epithelial organization of the adult neural stem cell niche, characterized by the apical surfaces of stem cells surrounded by ependymal cells in unique pinwheel structures.

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