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Transcriptional regulation of ependymal cell maturation within the postnatal brain.

ABSTRACT: BACKGROUND: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. FINDINGS: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. CONCLUSIONS: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.

SUBMITTER: Vidovic D

PROVIDER: S-EPMC5816376 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Transcriptional regulation of ependymal cell maturation within the postnatal brain.

Vidovic Diana D Davila Raul Ayala RA Gronostajski Richard M RM Harvey Tracey J TJ Piper Michael M

Neural development 20180216 1

<h4>Background</h4>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 t ...[more]

PMID: 29452604

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Project description:Spermatogenesis is the process by which male gametes are formed from a self-renewing population of spermatogonial stem cells (SSCs) residing in the testis. SSCs represent less than 1% of the total testicular cell population in adults, but must achieve a stable balance between self-renewal and differentiation. Once differentiation has occurred, the newly formed and highly proliferative spermatogonia must then enter the meiotic program in which DNA content is doubled, then halved twice to create haploid gametes. While much is known about the critical cellular processes that take place during the specialized cell division that is meiosis, much less is known about how the spermatocytes in the "first-wave" in juveniles compare to those that contribute to long-term, "steady-state" spermatogenesis in adults. Given the strictly-defined developmental process of spermatogenesis, this study explored the transcriptional profiles of developmental cell stages during testis maturation. Using a combination of comprehensive germ cell sampling with high-resolution, single-cell-mRNA-sequencing, we have generated a reference dataset of germ cell gene expression. We show that discrete developmental stages of spermatogenesis possess significant differences in the transcriptional profiles from neonates compared to juveniles and adults. Importantly, these gene expression dynamics are also reflected at the protein level in their respective cell types. We also show differential utilization of many biological pathways with age in both spermatogonia and spermatocytes, demonstrating significantly different underlying gene regulatory programs in these cell types over the course of testis development and spermatogenic waves. This dataset represents the first unbiased sampling of spermatogonia and spermatocytes during testis maturation, at high-resolution, single-cell depth. Not only does this analysis reveal previously unknown transcriptional dynamics of a highly transitional cell population, it has also begun to reveal critical differences in biological pathway utilization in developing spermatogonia and spermatocytes, including response to DNA damage and double-strand breaks.

Dataset Information

Transcriptional regulation of ependymal cell maturation within the postnatal brain.

Publications

Transcriptional regulation of ependymal cell maturation within the postnatal brain.

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