Transcriptional regulation of ependymal cell maturation within the postnatal brain

Abstract

BackgroundRadial glial stem cells within the developing nervous system generate a variety of post-mitotic cells, including neurons and glial cells, as well as the specialised multi-ciliated cells that line the walls of the ventricular system, the ependymal cells. Ependymal cells separate the brain parenchyma from the cerebrospinal fluid and mediate osmotic regulation, the flow of cerebrospinal fluid, and the subsequent dispersion of signalling molecules via the co-ordinated beating of their cilia. Deficits to ependymal cell development and function have been implicated in the formation of hydrocephalus, but the transcriptional mechanisms underpinning ependymal development remain poorly characterised.FindingsHere, we demonstrate that the transcription factor nuclear factor IX (NFIX) plays a central role in the development of the ependymal cell layer of the lateral ventricles. Expression of ependymal cell-specific markers is delayed in the absence of Nfix. Moreover, Nfix-deficient mice exhibit aberrant ependymal cell morphology at postnatal day 15, culminating in abnormal thickening and intermittent loss of this cell layer. Finally, we reveal Foxj1, a key factor promoting ependymal cell maturation, as a target for NFIX-mediated transcriptional activation.ConclusionsCollectively, our data indicate that ependymal cell development is reliant, at least in part, on NFIX expression, further implicating this transcription factor as a mediator of multiple aspects of radial glial biology during corticogenesis.Electronic supplementary materialThe online version of this article (10.1186/s13064-018-0099-4) contains supplementary material, which is available to authorized users.

Control of neurogenic competence in mammalian hypothalamic tanycytes

“…S4). Furthermore, a substantial reduction in the relative fraction of nonneuronal cells --including astrocytes, oligodendrocyte progenitor cells, and ependymal cells --is observed, in line with previous studies reporting an essential role for NFI family genes in gliogenesis in other CNS regions (14,(24)(25)(26). While controls show a higher fraction of tanycyte-derived astrocytes, a much higher fraction of GFP-positive cells are neurons in TKO mice (Fig.…”

Variants in nuclear factor I genes influence growth and development

“…In the dorsal telencephalon, Nfia, Nfib and Nfix are first expressed at embryonal day (E)11 within radial glia (Campbell et al, 2008;Mason, Piper, Gronostajski, & Richards, 2009;Plachez et al, 2008). They continue to be expressed in radial glia and ependymal cells, which arise from last radial glia (K. S. Chen, Harris, et al, 2017;Vidovic, Davila, Gronostajski, Harvey, & Piper, 2018). The expression patterns of the NFIA and NFIB proteins are initially similar, producing a high caudo-medial to low rostro-lateral gradient in the developing dorsal telencephalon in mice (Bunt, Lim, Zhao, Mason, & Richards, 2015).…”

“…Nfix knockout mice also exhibit dysmorphic hippocampal development, and commonly develop hydrocephaly around postnatal day 10, likely due to abnormal differentiation of radial glia into ependymal cells (Driller et al, 2007;Shu et al, 2003;Vidovic et al, 2018;Vidovic et al, 2015). Due to the lethality, feeding difficulties and frequent hydrocephaly, overgrowth is hard to determine in any of the Nfi homozygous knockout strains.…”

The investigation of hydrocephalus in mice lacking the transcription factor NFIX

“…Chromatin immunoprecipitation (ChIP) allows us to determine protein-binding sites on DNA. The fixed chromatin is sheared and immunoprecipitated with an antibody in this case we would use a specific NFIX antibody (Vidovic, Davila, Gronostajski, Harvey, & Piper, 2018). A powerful tool that when used correctly can provide valuable insight into the interactions of a specific gene.…”