In vertebrates, early brain development takes place at the expanded anterior end of the neural tube, which is filled with embryonic cerebrospinal fluid (E-CSF). Most of the proteins contained within the E-CSF, which play crucial roles in CNS development, are transferred from the blood serum. Two important questions are how E-CSF is manufactured and how its homeostasis is controlled. In this respect, the timing of the blood-CSF barrier formation is controversial. Recently, the concept of a functional dynamic barrier has been introduced. This type of barrier is different from that found in adults and is adapted to the specific requirements and environment of the developing nervous system. In this study, we injected a number of proteins into the outflow of the heart and into the cephalic cavities and examined their transport rate between these two embryo compartments. The results indicated that a functional blood-CSF barrier dynamically controls E-CSF protein composition and homeostasis in chick embryos before the formation of functional choroid plexuses. We also showed that proteins are transferred through transcellular routes in a specific area of the brain stem, close to the ventral mesencephalic and prosencephalic neuroectoderm, lateral to the ventral midline, in particular blood vessels. This study contributes to our understanding of the mechanisms involved in CNS development, as this blood-CSF interface regulates the composition of E-CSF by regulating its specific composition.
In vertebrates, brain development takes place at the expanded anterior end of the neural tube. After closure of the anterior neuropore, the brain wall forms a physiologically sealed cavity that encloses embryonic cerebrospinal fluid (E-CSF), a complex and protein-rich fluid. E-CSF has several crucial roles in brain anlagen development. In this respect, during the initiation of neurogenesis, increases in the volume of brain cavities account for 70% of the total growth of the brain primordium, and are accompanied by a parallel increase in E-CSF volume. Recently, we reported the presence of several blood vessels located in the brain stem lateral to the ventral midline, at the mesencephalon and prosencephalon level, which have a transient blood-CSF barrier function in chick embryos by transporting proteins in a selective manner via transcellular routes. These blood vessels control E-CSF protein composition and homeostasis during this early stage of CNS development, just after closure of the neuropores. Here we report that in chick and rat embryos these same blood vessels, which lie close to the neuroectoderm, express several molecules related to water and ion transport, namely AQP1, AQP4 and Kir4.1. Our results confirm that a blood-CSF barrier controls E-CSF composition and homeostasis from early stages of brain development in chick embryos, including water and ion influx, thus regulating E-CSF osmolarity. On the basis of our findings, we also propose that a similar blood-CSF barrier is present in mammals at equivalent developmental stages of the brain.
Global characterisation of proteins and the comparison between proteomes is providing new insights into general biological structures and processes, as well as between physiological and pathological conditions. During both embryonic development and adult life, brain cavities and ventricles are filled with a complex protein-rich fluid, the cerebrospinal fluid (CSF). In the last few years, it has been suggested that adult CSF has a key function as a fluid pathway for delivering diffusible signals to the brain, thus affecting the behaviour of specific brain parenchyma cells, particularly the putative neural stem cells. Accordingly, some pathologies that affect the central nervous system (CNS), such as neurodegenerative diseases and/or neurological disorders, are reflected in CSF protein content, either as a cause or as a consequence. Adult CSF is considered to be the successor of embryonic CSF (E-CSF). Most of the proteins contained within E-CSF, as analysed in avians (chick) and mammals (rat and human), are also detected in adult humans, suggesting that some of their roles in CNS cell behaviour are similar. Despite the heterogeneity of the currently available data, which is due to technical differences in the proteomic analyses, the use of different model systems and the great variety of sample sources, it is increasingly clear that this fluid regulates the behaviour of neural stem cells throughout development and during adult life, thus suggesting a possible approach to brain cell therapies. This review focuses on current data regarding CSF proteomes in relation to CSF functions in both physiological and pathological conditions, as well as on CSF manufacture.
During embryonic development and adult life, brain cavities and ventricles are filled with cerebrospinal fluid (CSF). CSF has attracted interest as an active signaling medium that regulates brain development, homeostasis and disease. CSF is a complex protein-rich fluid containing growth factors and signaling molecules that regulate multiple cell functions in the central nervous system (CNS). The composition and substance concentrations of CSF are tightly controlled. In recent years, it has been demonstrated that embryonic CSF (eCSF) has a key function as a fluid pathway for delivering diffusible signals to the developing brain, thus contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the expansion and patterning of the brain. From fetal stages through to adult life, CSF is primarily produced by the choroid plexus. The development and functional activities of the choroid plexus and other blood–brain barrier (BBB) systems in adults and fetuses have been extensively analyzed. However, eCSF production and control of its homeostasis in embryos, from the closure of the anterior neuropore when the brain cavities become physiologically sealed, to the formation of the functional fetal choroid plexus, has not been studied in as much depth and remains open to debate. This review brings together the existing literature, some of which is based on experiments conducted by our research group, concerning the formation and function of a temporary embryonic blood–CSF barrier in the context of the crucial roles played by the molecules in eCSF.
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