Transcriptional regulation of ependymal cell maturation within the postnatal brain

Diana Vidovic, Raul Ayala Davila, Richard M. Gronostajski, Tracey J. Harvey, Michael Piper

Radial 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. Here, 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. Collectively, 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.