Spatially Heterogeneous Choroid Plexus Transcriptomes Encode Positional Identity and Contribute to Regional CSF Production

A sheet of choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors into the CSF. To evaluate whether differences in the CSF proteome across ventricles arise, in part, from regional differences in choroid plexus gene expression, we defined the transcriptome of lateral ventricle (telencephalic) versus fourth ventricle (hindbrain) choroid plexus. We find that positional identities of mouse, macaque, and human choroid plexi derive from gene expression domains that parallel their axial tissues of origin. We then show that molecular heterogeneity between telencephalic and hindbrain choroid plexi contributes to region-specific, age-dependent protein secretion in vitro. Transcriptome analysis of FACS-purified choroid plexus epithelial cells also predicts their cell-type-specific secretome. Spatial domains with distinct protein expression profiles were observed within each choroid plexus. We propose that regional differences between choroid plexi contribute to dynamic signaling gradients across the mammalian cerebroventricular system.

• Publication year

  2015

• Venue

  Journal of Neuroscience

• Publication date

  2015-03-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1523/JNEUROSCI.3081-14.2015PMID 25810521PMCID PMC4389594
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A new look at cerebrospinal fluid circulation

  2014cited by this paper
• Astrocyte-encoded positional cues maintain sensorimotor circuit integrity

  2014cited by this paper
• A new look at cerebrospinal fluid circulation

  2014cited by this paper
• Count-based differential expression analysis of RNA sequencing data using R and Bioconductor

  2013cited by this paper
• Mechanisms That Determine the Internal Environment of the Developing Brain: A Transcriptomic, Functional and Ultrastructural Approach

  2013cited by this paper
• Isolation of cerebrospinal fluid from rodent embryos for use with dissected cerebral cortical explants.

  2013influential reference
• The Choroid Plexus and Cerebrospinal Fluid: Emerging Roles in Development, Disease, and Therapy

  2013cited by this paper
• Cerebrospinal fluid secretion by the choroid plexus.

  2013influential reference
• Sleep Drives Metabolite Clearance from the Adult Brain

  2013cited by this paper
• Direct Proteomic Quantification of the Secretome of Activated Immune Cells

  2013cited by this paper
• Hox genes: choreographers in neural development, architects of circuit organization.

  2013cited by this paper
• Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis.

  2013influential reference
• Increased in Vivo Amyloid-β42 Production, Exchange, and Loss in Presenilin Mutation Carriers

  2013cited by this paper
• The cerebrospinal fluid: regulator of neurogenesis, behavior, and beyond

  2012cited by this paper
• Molecular Characterisation of Transport Mechanisms at the Developing Mouse Blood–CSF Interface: A Transcriptome Approach

  2012cited by this paper
• BMP4 Sufficiency to Induce Choroid Plexus Epithelial Fate from Embryonic Stem Cell-Derived Neuroepithelial Progenitors

  2012cited by this paper
• Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks

  2012cited by this paper
• Integrating diverse genomic data using gene sets

  2011cited by this paper
• Transcriptome signature of the adult mouse choroid plexus

  2011cited by this paper
• Neurogenesis at the brain-cerebrospinal fluid interface.

  2011cited by this paper
• The cerebrospinal fluid provides a proliferative niche for neural progenitor cells.

  2011cited by this paper
• Differential expression analysis for sequence count data

  2010cited by this paper
• Sonic hedgehog is required for vascular outgrowth in the hindbrain choroid plexus.

  2010influential reference
• Adult SVZ lineage cells home to and leave the vascular niche via differential responses to SDF1/CXCR4 signaling.

  2010cited by this paper
• Transventricular delivery of Sonic hedgehog is essential to cerebellar ventricular zone development

  2010cited by this paper
• Sonic hedgehog signaling regulates a novel epithelial progenitor domain of the hindbrain choroid plexus

  2009influential reference
• Totally tubular: the mystery behind function and origin of the brain ventricular system

  2009cited by this paper
• Mechanisms of regulated unconventional protein secretion

  2009cited by this paper
• Transthyretin mouse transgenes direct RFP expression or Cre‐mediated recombination throughout the visceral endoderm

  2009cited by this paper
• TWIST-1 is overexpressed in neoplastic choroid plexus epithelial cells and promotes proliferation and invasion.

  2009cited by this paper
• Cerebrospinal Fluid Research BioMed Central Review Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

  2008cited by this paper
• Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists

  2008influential reference
• A specialized vascular niche for adult neural stem cells.

  2008cited by this paper
• Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources

  2008influential reference
• Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

  2008cited by this paper
• Prenatal Mouse Brain Atlas

  2008cited by this paper
• A transgenic FOXJ1-Cre system for gene inactivation in ciliated epithelial cells.

  2007cited by this paper
• Molecularly and temporally separable lineages form the hindbrain roof plate and contribute differentially to the choroid plexus

  2007cited by this paper
• A global double‐fluorescent Cre reporter mouse

  2007cited by this paper
• A comparative proteomic analysis of human and rat embryonic cerebrospinal fluid.

  2007influential reference
• Regulatory constraints in the evolution of the tetrapod limb anterior–posterior polarity

  2006cited by this paper
• Human amyloid-β synthesis and clearance rates as measured in cerebrospinal fluid in vivo

  2006cited by this paper
• Proteome analysis of chick embryonic cerebrospinal fluid

  2006cited by this paper
• Direct and indirect roles of CNS dorsal midline cells in choroid plexus epithelia formation

  2005cited by this paper
• The choroid plexus in the rise, fall and repair of the brain

  2005cited by this paper
• Early developmental arrest of mammalian limbs lacking HoxA/HoxD gene function

  2005cited by this paper
• Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation

  2003influential reference
• Development of the choroid plexus

  2001cited by this paper
• Vascular niche for adult hippocampal neurogenesis

  2000cited by this paper
• Area identity shifts in the early cerebral cortex of Emx2−/− mutant mice

  2000cited by this paper
• Expression patterns of homeobox and other putative regulatory genes in the embryonic mouse forebrain suggest a neuromeric organization.

  1993cited by this paper
• A morphometric study on the development of the lateral ventricle choroid plexus, choroid plexus capillaries and ventricular ependyma in the rat.

  1990cited by this paper
• An experimental and ultrastructural study on the development of the avian choroid plexus

  1989cited by this paper
• Comparison of proteins in CSF of lateral and IVth ventricles during early development of fetal sheep.

  1983influential reference
• A morphological study of the development of the mouse choroid plexus.

  1979cited by this paper
• The development of the paraphysis cerebri in man with comments on its relationship to the inter‐columnar tubercle and its significance for the origin of cystic tumors in the third ventricle

  1955cited by this paper
• Article Endothelial Nt-3 Delivered by Vasculature and Csf Promotes Quiescence of Subependymal Neural Stem Cells through Nitric Oxide Induction

  year unknowncited by this paper

• Choroid Plexus Modulates Subventricular Zone Adult Neurogenesis and Olfaction Through Secretion of Small Extracellular Vesicles

  2025cites this paper
• The transcriptome of the ovine choroid plexus is regulated by thyroid hormone but not by photoperiod.

  2025cites this paper
• Integrative genomics elucidates the evolutionary, temporal, and developmental origins of a hydrocephalus risk gene

  2025cites this paper
• Can optic nerve morphology in children with autism spectrum disorder be associated with atypical visual-sensory behaviors?

  2025cites this paper
• Novel Insights into Emx2 and Dmrta2 Cooperation during Cortex Development and Evidence for Dmrta2 Function in the Choroid Plexus

  2025cites this paper
• Choroid plexus-mediated CSF secretion remains stable in aging rats via high and age-resistant metabolic activity

  2025cites this paper
• The influence of the choroid plexus on brain function: beyond its role in cerebrospinal fluid production

  2025influential citation
• Subject-specific variability in cerebrospinal fluid flow characteristics through cerebral aqueducts in a healthy population: a magnetic resonance imaging and computational investigation

  2025cites this paper
• Molecular hallmarks of hydrocephalus.

  2025cites this paper
• Sequential emergence and contraction of epithelial subtypes in the prenatal human choroid plexus revealed by a stem cell model

  2025cites this paper
• SPINT1 Expressed in Epithelial Cells of Choroid Plexus in Human and Mouse Brains

  2025cites this paper
• Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development

  2025cites this paper
• Sex-related differences and associated transcriptional signatures in the brain ventricular system and cerebrospinal fluid development in full-term neonates

  2025cites this paper
• IGFBP-2 and IGF-II: Key Components of the Neural Stem Cell Niche? Implications for Glioblastoma Pathogenesis

  2025influential citation
• Global Clock Coordination by the Brain Clock in the Suprachiasmatic Nucleus Through Relay and Amplification of Diffusible and Neural Signaling

  2025cites this paper
• The glutathione-dependent neuroprotective activity of the blood-CSF barrier is inducible through the Nrf2 signaling pathway during postnatal development

  2025cites this paper
• Hydrocephalus Pathophysiology and Epidemiology.

  2025cites this paper
• Proteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation

  2024cites this paper
• Role of immature choroid plexus in the pathology of model mice and human iPSC-derived organoids with autism spectrum disorder.

  2024cites this paper
• Differential Lipid Signatures of Lumbar and Cisternal Cerebrospinal Fluid

  2024cites this paper
• CAP superfamily proteins in human: a new target for cancer therapy

  2024cites this paper
• Cilia dysfunction in the lateral ventricles after neonatal intraventricular hemorrhage does not lead to functional changes in cilia-based CSF flow networks

  2024cites this paper
• Demyelination and Impaired Oligodendrogenesis in the Corpus Callosum Following Lead Exposure.

  2024cites this paper
• The choroid plexus maintains adult brain ventricles and subventricular zone neuroblast pool, which facilitates poststroke neurogenesis

  2024cites this paper
• BioLuminescent OptoGenetics in the choroid plexus: integrated opto- and chemogenetic control in vivo

  2024cites this paper
• The evolutionarily conserved choroid plexus contributes to the homeostasis of brain ventricles in zebrafish.

  2024cites this paper
• Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2

  2024cites this paper
• The circadian clock in the choroid plexus drives rhythms in multiple cellular processes under the control of the suprachiasmatic nucleus

  2024cites this paper
• ERK signaling expands mammalian cortical radial glial cells and extends the neurogenic period

  2024cites this paper
• Outcomes of the 2019 hydrocephalus association workshop, "Driving common pathways: extending insights from posthemorrhagic hydrocephalus"

  2023cites this paper
• Establishing Hedgehog Gradients during Neural Development

  2023cites this paper
• E-Cadherin Is Expressed in Epithelial Cells of the Choroid Plexus in Human and Mouse Brains

  2023cites this paper
• Dual function of the choroid plexus: Cerebrospinal fluid production and control of brain ion homeostasis.

  2023cites this paper
• ERK signaling drives evolutionary expansion of the mammalian cerebral cortex

  2023cites this paper
• Cerebrospinal fluid-contacting neurons: multimodal cells with diverse roles in the CNS

  2023cites this paper
• Towards an Understanding of Microglia and Border-Associated Macrophages

  2023cites this paper
• [Polymodal sensory integration at the interface with the cerebrospinal fluid].

  2023cites this paper
• Nocturnal increase in cerebrospinal fluid secretion as a circadian regulator of intracranial pressure

  2023cites this paper
• Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2

  2023cites this paper
• BMP7 expression in mammalian cortical radial glial cells increases the length of the neurogenic period

  2023cites this paper
• Biomechanical effects of hyper-dynamic cerebrospinal fluid flow through the cerebral aqueduct in idiopathic normal pressure hydrocephalus patients.

  2023cites this paper
• Local angiogenic interplay of Vegfc/d and Vegfa controls brain region-specific emergence of fenestrated capillaries

  2023cites this paper
• Choroid Plexus Modulates Subventricular Zone Adult Neurogenesis and Olfaction Through Secretion of Small Extracellular Vesicles

  2023cites this paper
• Genome-wide methylation analysis of circulating tumor DNA: A new biomarker for recurrent glioblastom

  2023cites this paper
• Morphological and mitochondrial changes in murine choroid plexus epithelial cells during healthy aging

  2023cites this paper
• Impact of in vivo cyclic reprogramming on the choroid plexus

  2023influential citation
• SCO-spondin knockout mice exhibit small brain ventricles and mild spine deformation

  2023cites this paper
• Local angiogenic interplay of Vegfc/d and Vegfa drives brain region-specific development of fenestrated capillaries

  2023cites this paper
• Cerebrospinal fluid production by the choroid plexus: a century of barrier research revisited

  2022cites this paper
• Acetazolamide modulates intracranial pressure directly by its action on the cerebrospinal fluid secretion apparatus

  2022cites this paper
• Regulatory heterogeneity of Vegf- and Wnt7-dependent angiogenesis drives phenotypic diversity of brain vasculature

  2022cites this paper
• Cobalt Neurotoxicity: Transcriptional Effect of Elevated Cobalt Blood Levels in the Rodent Brain

  2022cites this paper
• Organization of the ventricular zone of the cerebellum

  2022influential citation
• Secondary Brain Injury Following Neonatal Intraventricular Hemorrhage: The Role of the Ciliated Ependyma

  2022cites this paper
• Experimental approaches for manipulating choroid plexus epithelial cells

  2022cites this paper
• Regulation of choroid plexus development and its functions

  2022cites this paper
• Immortalized human choroid plexus endothelial cells enable an advanced endothelial-epithelial two-cell type in vitro model of the choroid plexus

  2022cites this paper
• Transcriptional profiling of transport mechanisms and regulatory pathways in rat choroid plexus

  2022cites this paper
• OTX2 Homeoprotein Functions in Adult Choroid Plexus

  2021influential citation
• Roof Plate in Cerebellar Neurogenesis

  2021cites this paper
• Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development

  2021cites this paper
• SOX9-COL9A3–dependent regulation of choroid plexus epithelial polarity governs blood–cerebrospinal fluid barrier integrity

  2021cites this paper
• Pluripotent stem cell-derived epithelium misidentified as brain microvascular endothelium requires ETS factors to acquire vascular fate

  2021cites this paper
• Assessment of common housekeeping genes as reference for gene expression studies using RT-qPCR in mouse choroid plexus

  2021cites this paper
• Multifaceted microglia — key players in primary brain tumour heterogeneity

  2021cites this paper
• Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease

  2021cites this paper
• Molecular mechanisms of brain water transport

  2021cites this paper
• Multi-omic analysis elucidates the genetic basis of hydrocephalus

  2021cites this paper
• MEIS-WNT5A axis regulates development of fourth ventricle choroid plexus.

  2021cites this paper
• From seed to flower: blossoming of microglia in development and brain repair

  2021cites this paper
• Breaking the barrier: In vitro models to study choroid plexus development.

  2021cites this paper
• Macrophages on the margin: choroid plexus immune responses.

  2021cites this paper
• 3D Reconstruction of the Clarified Rat Hindbrain Choroid Plexus

  2021cites this paper
• Regulation of prefrontal patterning and connectivity by retinoic acid

  2021cites this paper
• Identification of a choroid plexus vascular barrier closing during intestinal inflammation

  2021cites this paper
• Brain transcriptome analysis of a CLN2 mouse model as a function of disease progression

  2021cites this paper
• Modification of gene expression and soluble factor secretion in the lateral ventricle choroid plexus: Analysis of the impacts on the neocortical development.

  2021cites this paper
• Immunohistochemical expression of osteopontin and collagens in choroid plexus of human brains

  2021cites this paper
• A cellular and spatial map of the choroid plexus across brain ventricles and ages.

  2021cites this paper
• Advancing brain barriers RNA sequencing: guidelines from experimental design to publication

  2020influential citation
• Iron accumulation in the choroid plexus, ependymal cells and CNS parenchyma in a rat strain with low‐grade haemolysis of fragile macrocytic red blood cells

  2020cites this paper
• Ependyma

  2020cites this paper
• Pharmacological properties of TRPM3 isoforms are determined by the length of the pore loop

  2020cites this paper
• Neuroimaging in Pediatric Hydrocephalus

  2020cites this paper
• Non-canonical, potassium-driven cerebrospinal fluid clearance

  2020cites this paper
• Human CNS barrier-forming organoids with cerebrospinal fluid production

  2020cites this paper
• Roles of the Choroid Plexus in Aging

  2020cites this paper
• MEIS-WNT5A axis regulates development of 4th ventricle choroid plexus

  2020cites this paper
• Three-Dimensional Explant Platform for Studies on Choroid Plexus Epithelium

  2020cites this paper
• Role of the Choroid Plexus in Health and Disease

  2020cites this paper
• ZFP423 regulates early patterning and multiciliogenesis in the hindbrain choroid plexus

  2020cites this paper
• Method for Primary Epithelial Cell Culture from the Rat Choroid Plexus.

  2020cites this paper
• CRISPLD1: a novel conserved target in the transition to human heart failure

  2020cites this paper
• Emergence and Developmental Roles of the Cerebrospinal Fluid System.

  2020cites this paper
• WNT5a Regulates Epithelial Morphogenesis in the Developing Choroid Plexus.

  2020cites this paper
• Constitutive activation of canonical Wnt signaling disrupts choroid plexus epithelial fate

  2020cites this paper
• Glioma-derived IL-33 orchestrates an inflammatory brain tumor microenvironment that accelerates glioma progression

  2020cites this paper
• Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface.

  2020cites this paper
• SARS-CoV-2 infects brain choroid plexus and disrupts the blood-CSF-barrier

  2020cites this paper
• Targeting the Choroid Plexuses for Protein Drug Delivery

  2020cites this paper