Presentation description

The meninges are a multilayered, vascularized set of membranes that surround and protect the Central Nervous System. Despite life-threatening pathologies such as meningitis and meningiomas accounting for nearly 250,000 deaths each year, we have a limited understanding of meningeal biology. Our lab studies Fluorescent Granular Perithelial Cells (FGPs), a meningeal cell population analogous to mammalian perivascular macrophages (PVMs) that associate with meningeal blood vessels. Notably, FGPs express the enzyme lysyl oxidase (LOX) Loxl1, known to induce vessel formation (known as 'angiogenesis') in other systems. Previous treatment of zebrafish embryos with the pan-LOX inhibitor β-aminopropionitrile (BAPN) resulted in decreased vascular density, leading us to hypothesize that FGPs contribute to meningeal angiogenesis via Loxl1 in developing zebrafish. However, BAPN is known to cause off-target effects in several tissues, including blood vessels. To prevent this, we treated transgenic zebrafish embryos with labeled blood vessels and FGPs against different doses of the pan-LOX inhibitor PXS-4787, which is less prone to cause off-target effects. We then imaged the treated embryos using confocal microscopy to visualize and record meningeal vasculature density changes. Preliminary results indicate a slight decrease in meningeal vascular density after PXS-4787 treatment compared to BAPN, suggesting that decreased vasculature from BAPN treatment may be caused by off-target effects, putting into question whether LOX activity is required for early vascular development. By dissecting the roles of FGPs and LOX activity in meningeal vascular development, our work aims to address the longstanding gap in knowledge about the mechanisms underlying meningeal vascular regulation.