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Derk, J.

Publications and source records attributed to Derk, J..

2 recordsLinked to original sources
bioRxiv2024

Newly discovered base barrier cells provide compartmentalization of choroid plexus, brain and CSF

The choroid plexus (ChP) is a highly understudied structure of the central nervous system (CNS). The structure hangs in the brain ventricles, is composed of an epithelial cell layer, which produces the cerebrospinal fluid (CSF) and forms the blood-CSF barrier. It encapsulates a stromal mix of fenestrated capillaries, fibroblasts and a broad range of immune cells. Here, we report that the ChP base region harbors unique fibroblasts that cluster together, are connected by tight junctions and seal the ChP stroma from brain and CSF, thereby forming ChP base barrier cells (ChP BBCs). ChP BBCs are derived from meningeal mesenchymal precursors, arrive early during embryonic development, are maintained throughout life and are conserved across species. Moreover, we provide transcriptional profiles and key markers to label ChP BBCs and observe a striking transcriptional similarity with meningeal arachnoid barrier cells (ABCs). Finally, we provide evidence that this fibroblast cluster functions as a barrier to control communication between CSF and the ChP stroma and between the latter and the brain parenchyma. Moreover, loss of barrier function was observed during an inflammatory insult. Altogether, we have identified a novel barrier that provides functional compartmentalization of ChP, brain and CSF. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/601696v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@181e787org.highwire.dtl.DTLVardef@1875f33org.highwire.dtl.DTLVardef@7b2bcdorg.highwire.dtl.DTLVardef@78baa6_HPS_FORMAT_FIGEXP M_FIG Newly discovered base barrier cells provide compartmentalization of choroid plexus, brain and CSF The choroid plexus (ChP) hangs in the brain ventricles and is composed of an epithelial cell layer which produces the cerebrospinal fluid (CSF) and forms the blood-CSF barrier. The ChP epithelial cells are continuous with the ependymal cells lining the ventricle wall. At this base region, we identified and characterized a novel subtype of fibroblasts coined the ChP base barrier cells (BBCs). ChP BBCs express tight junctions (TJs), cluster together and seal the ChP stroma from CSF and brain parenchyma. The subarachnoid space (SAS) CSF penetrates deep into choroid plexus invaginations where it is halted by ChP BBCs. Abbreviations: E9-16.5 (embryonic day 9-16.5); P1-4 (postnatal day 1-4). C_FIG

neuroscience↗
bioRxiv2022

Formation and function of the meninges arachnoid barrier around the developing brain

Barriers at the level of the brain endothelium, choroid plexus, and meninges strictly regulate movement of molecules and cells into and out of the central nervous system (CNS). In contrast to the blood-brain barrier and choroid plexus epithelial barrier, developmental timing and function of the meningeal arachnoid barrier, a layer of epithelial-like cells connected by tight and adherens junctions, is largely unknown. To begin to address this, we mined our E14.5 mouse single cell transcriptomic (scRNA-seq) meningeal fibroblast data set and identified the repression of Wnt-{beta}-catenin signaling as a key mechanism underlying the specification of epithelial-like arachnoid barrier cells from Collagen 1+ and Crabp2+ mesenchymal meningeal precursors. We show that elevating Wnt-{beta}-catenin signaling in prenatal meningeal mesenchymal cells prevented the development of arachnoid barrier cells. In the absence of dorsal arachnoid barrier cells, the prenatal meninges and brain are penetrable to biocytin-TMR and Streptococcus agalactiae (Group B Streptococcus, GBS), the leading pathogen known to drive life-threatening neonatal meningitis. We show that a layer of Claudin 11 (tight junction) and E-cadherin (adherens junction) expressing arachnoid barrier cells appear around the mouse brain from E13-E15 and the emergence of a functional barrier by E17 coincides with junctional localization of Claudin 11. Postnatal growth of the arachnoid barrier is marked initially by proliferation and later re-organization of junctional domains. This work provides fundamental knowledge on development and prenatal function of a meningeal arachnoid barrier, and novel tools for future studies on regional functions of this CNS barrier in the meninges.

developmental biology↗