The choroid plexus (ChP) is an extensively vascularized tissue that protrudes into the brain ventricular system of all vertebrates. This highly specialized structure, consisting of the polarized epithelial sheet and underlying stroma, serves a spectrum of functions within the central nervous system (CNS), most notably the production of cerebrospinal fluid (CSF). The epithelial cells of the ChP have the competence to tightly modulate the biomolecule composition of CSF, which acts as a milieu functionally connecting ChP with other brain structures. This review aims to eloquently summarize the current knowledge about the development of ChP. We describe the mechanisms that control its early specification from roof plate followed by the formation of proliferative regions-cortical hem and rhombic lips-feeding later development of ChP. Next, we summarized the current knowledge on the maturation of ChP and mechanisms that control its morphological and cellular diversity. Furthermore, we attempted to review the currently available battery of molecular markers and mouse strains available for the research of ChP, and identified some technological shortcomings that must be overcome to accelerate the ChP research field. Overall, the central principle of this review is to highlight ChP as an intriguing and surprisingly poorly known structure that is vital for the development and function of the whole CNS. We believe that our summary will increase the interest in further studies of ChP that aim to describe the molecular and cellular principles guiding the development and function of this tissue.

• Klíčová slova
• Cerebrospinal fluid (CSF), ChP epithelial cells, Choroid plexus (ChP), Cortical hem, Morphogenesis, Rhombic lips,
• MeSH
• centrální nervový systém * MeSH
• epitelové buňky MeSH
• mozek MeSH
• myši MeSH
• plexus chorioideus * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The choroid plexus (ChP) produces cerebrospinal fluid and forms an essential brain barrier. ChP tissues form in each brain ventricle, each one adopting a distinct shape, but remarkably little is known about the mechanisms underlying ChP development. Here, we show that epithelial WNT5A is crucial for determining fourth ventricle (4V) ChP morphogenesis and size in mouse. Systemic Wnt5a knockout, or forced Wnt5a overexpression beginning at embryonic day 10.5, profoundly reduced ChP size and development. However, Wnt5a expression was enriched in Foxj1-positive epithelial cells of 4V ChP plexus, and its conditional deletion in these cells affected the branched, villous morphology of the 4V ChP. We found that WNT5A was enriched in epithelial cells localized to the distal tips of 4V ChP villi, where WNT5A acted locally to activate non-canonical WNT signaling via ROR1 and ROR2 receptors. During 4V ChP development, MEIS1 bound to the proximal Wnt5a promoter, and gain- and loss-of-function approaches demonstrated that MEIS1 regulated Wnt5a expression. Collectively, our findings demonstrate a dual function of WNT5A in ChP development and identify MEIS transcription factors as upstream regulators of Wnt5a in the 4V ChP epithelium.

• Klíčová slova
• Choroid plexus, Epithelium, Meis1, Meis2, Morphogenesis, WNT5a,
• MeSH
• buněčné linie MeSH
• CRISPR-Cas systémy genetika   MeSH
• čtvrtá mozková komora embryologie   MeSH
• epitel metabolismus   MeSH
• epitelové buňky metabolismus   MeSH
• HEK293 buňky MeSH
• lidé MeSH
• mozek embryologie   MeSH
• myši knockoutované MeSH
• myši MeSH
• plexus chorioideus embryologie   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• protein Wnt 5a genetika   metabolismus   MeSH
• signální transdukce fyziologie   MeSH
• sirotčí receptory podobné receptoru tyrosinkinasy metabolismus   MeSH
• transkripční faktor Meis1 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• Meis1 protein, mouse MeSH Prohlížeč
• protein Wnt 5a MeSH
• Ror1 protein, mouse MeSH Prohlížeč
• Ror2 protein, mouse MeSH Prohlížeč
• sirotčí receptory podobné receptoru tyrosinkinasy MeSH
• transkripční faktor Meis1 MeSH
• Wnt5a protein, mouse MeSH Prohlížeč

Cerebrospinal fluid (CSF) is the liquid that fills the brain ventricles. CSF represents not only a mechanical brain protection but also a rich source of signalling factors modulating diverse processes during brain development and adulthood. The choroid plexus (CP) is a major source of CSF and as such it has recently emerged as an important mediator of extracellular signalling within the brain. Growing interest in the CP revealed its capacity to release a broad variety of bioactive molecules that, via CSF, regulate processes across the whole central nervous system (CNS). Moreover, CP has been also recognized as a sensor, responding to altered composition of CSF associated with changes in the patterns of CNS activity. In this review, we summarize the recent advances in our understanding of the CP as a signalling centre that mediates long-range communication in the CNS. By providing a detailed account of the CP secretory repertoire, we describe how the CP contributes to the regulation of the extracellular environment-in the context of both the embryonal as well as the adult CNS. We highlight the role of the CP as an important regulator of CNS function that acts via CSF-mediated signalling. Further studies of CP-CSF signalling hold the potential to provide key insights into the biology of the CNS, with implications for better understanding and treatment of neuropathological conditions.

• Klíčová slova
• cerebrospinal fluid, choroid plexus, secretion,
• MeSH
• biologický transport fyziologie   MeSH
• hematoencefalická bariéra metabolismus   MeSH
• lidé MeSH
• plexus chorioideus metabolismus   MeSH
• signální transdukce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

WNTs are lipid-modified proteins that control multiple functions in development and disease via short- and long-range signaling. However, it is unclear how these hydrophobic molecules spread over long distances in the mammalian brain. Here we show that WNT5A is produced by the choroid plexus (ChP) of the developing hindbrain, but not the telencephalon, in both mouse and human. Since the ChP produces and secretes the cerebrospinal fluid (CSF), we examine the presence of WNT5A in the CSF and find that it is associated with lipoprotein particles rather than exosomes. Moreover, since the CSF flows along the apical surface of hindbrain progenitors not expressing Wnt5a, we examined whether deletion of Wnt5a in the ChP controls their function and find that cerebellar morphogenesis is impaired. Our study thus identifies the CSF as a route and lipoprotein particles as a vehicle for long-range transport of biologically active WNT in the central nervous system.

• MeSH
• biologický transport MeSH
• lidé MeSH
• lipoproteiny mozkomíšní mok   MeSH
• morfogeneze MeSH
• myši inbrední ICR MeSH
• plexus chorioideus metabolismus   MeSH
• protein Wnt 5a genetika   metabolismus   MeSH
• rombencefalon embryologie   metabolismus   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lipoproteiny MeSH
• protein Wnt 5a MeSH
• WNT5A protein, human MeSH Prohlížeč
• Wnt5a protein, mouse MeSH Prohlížeč