Work in the zebrafish and other models has highlighted important roles for lyve1, ccbe1, and other genes in lymphatic development ( Hogan et al., 2009 Okuda et al., 2012). The Prox1 gene is regarded as a lymphatic ‘master regulator’ based on a series of studies performed in mouse, zebrafish, Xenopus and chick ( Hong et al., 2002 Oliver and Harvey, 2002 Peyrot et al., 2010 Rodriguez-Niedenführ et al., 2001 Wigle et al., 2002 Wigle and Oliver, 1999 Yaniv et al., 2006).

Molecular characterization has led to the identification of genes essential for lymphatic development. Lymphedema results from a failure to drain interstitial fluid via the lymphatics, leading to severe edema of the tissues, and is one of the most common secondary effects of cancer-related prophylactic surgeries and treatments ( Armer and Stewart, 2005 Poage et al., 2008). Defects in the development or function of the lymphatic system can lead to embryonic death, or to debilitating lymphedema in children and adults. The lymphatic system is critical for fluid homeostasis, lipid absorption, and reincorporation of macromolecules extravasated into the interstitial spaces of tissues back into the circulation. The blood vascular (circulatory) system transports nutrients, oxygen, hormonal signals, and immune cells throughout the body. Homeostatic balance in an organism relies on the adequate function of specialized organs and systems including the blood and lymphatic vasculature. Our findings provide the first report of a perivascular cell population in the brain derived from vascular endothelium. Despite their macrophage-like morphology and perivascular location, zebrafish FGPs appear molecularly most similar to lymphatic endothelium, and our imaging studies suggest that these cells emerge by differentiation from endothelium of the optic choroidal vascular plexus. Based on similarities in their morphology, location, and scavenger behavior, these cells appear to be the zebrafish equivalent of cells variably characterized as Fluorescent Granular Perithelial cells (FGPs), perivascular macrophages, or ‘Mato Cells’ in mammals.

Here, we describe a novel perivascular cell population closely associated with blood vessels on the zebrafish brain. Perivascular cells surrounding brain blood vessels are thought to be important for blood-brain barrier establishment, but their roles are not well defined.

The blood-brain barrier is essential for the proper homeostasis and function of the CNS, but its mechanism of function is poorly understood.

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