Presentation description

The meninges are layers of connective tissue that envelop the Central Nervous system, protecting it from mechanical shock, controlling fluid homeostasis, and supporting blood supply and immune surveillance. Despite these important roles, little is known about the development, composition, and functions of the meninges. Primarily studied in mammals; where they lay just under the skull, making in vivo studies on live developing animals sometimes challenging. The zebrafish represents a powerful alternative research organism to study meningeal structures as they have an anatomically conserved, multilayer meninges similar to mammals, and a thin transparent skull that facilitates in vivo studies at embryonic and adult stages of development. We are investigating the function of the Lysyl Oxidase Like-1 (Loxl1), an essential enzyme for the biogenesis of collagen and elastin, essential elements of the meninges. Single Cell RNA-seq of entire meninges revealed that loxl1 is expressed by fluorescent granular perithelial cells (FGPs), a perivascular meningeal population known to filter cerebrospinal fluid and promote angiogenesis, however their role in the biogenesis of connective tissue has never been explored. We hypothesized that FGPs-expressed loxl1 could play a role in establishing the balance of collagen and elastin in the meninges. To test this, we have optimized a safe working concentration of the Loxl1 inhibitor Beta-aminopropionitrile (BAPN) effective in zebrafish embryos, and currently are applying this drug to FGP-labelled transgenic animals to determine its effect on the development and function of the meninges.