Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia
Perivascular cells of the vertebrate brain maintain vascular integrity, modulate vessel function, contribute in stroke and are involved in the maintenance of neural stem cells. Despite these functions, the origins, diversity and many roles of perivascular cells remain to be fully understood. Using transgenic zebrafish, we identified a novel population of isolated lymphatic endothelial cells that are perivascular, surrounding blood vessels within the zebrafish meninges. These meningeal perivascular lymphatic endothelial cells (pvLECs) express LEC specific markers and form by lymphangiogenic sprouting from blood vessels. pvLEC development requires normal and dose-dependent signaling through the vegfc/vegfd/ccbe1/vegfr3 pathway. During development, pvLECs develop from a continuous lymphatic endothelial loop in the midbrain periphery, into a dispersed, non-lumenized, perivascular lineage. These cells produce vascular endothelial growth factors and are essential for normal angiogenesis of blood vessels within the meninges. Together, these data identify an unexpected lymphatic lineage and developmental mechanism that is necessary for establishment of a normal meningeal blood vasculature.