The close anatomic apposition between nerves and vessels is critical for their functional interdependence, and revealing the signals that mediate the tight neurovascular association provides insights into our understanding of nervous system function. This is more evident in the brain where neural cells (neurons and glia) and vascular cells (endothelia and pericytes) form a functionally

integrated network that is collectively termed the neurovascular unit (Iadecola, 2004). Neurovascular unit integrity has recently been shown to regulate important physiological functions and is linked to the onset and progression of various Selleck Caspase inhibitor neurodegenerative diseases. For example, a deficient endothelial-secreted see more PDGF-BB-PDGFβ signaling on pericytes within the vascular

system leads to defects in cerebrovascular integrity and, subsequently, results in neuronal dysfunction (Armulik et al., 2010, Bell et al., 2010 and Daneman et al., 2010). Similarly, a recent study shows that deficient signaling between astrocyte-secreted apoE, a major risk factor for Alzheimer’s disease, and its binding protein LRP1 on pericytes can also lead to cerebrovascular defects followed by neuronal degeneration (Bell et al., 2012). The functional consequences of periphery neurovascular congruency defects on nervous system function are less understood. In the whisker system, earlier studies suggest that the vascular component Vasopressin Receptor affiliated with each whisker both affects the movement of the whisker

and modulates the sensitivity of the sensory nerve endings (Fundin et al., 1997 and Wineski, 1985). It will be an important future direction to use the animal model we have generated here to investigate whether developmental deficits in establishing neurovascular patterning in the whisker pad target areas will manifest as functional and behavioral deficits in the mature animals. Both the peripheral TG and higher level barrel cortical electrophysiological properties in response to whiskering can be used as neural functional readouts. It will also be interesting to examine functional consequence of neurovascular congruency defects in other peripheral examples such as forelimb skin sensory axon/arterial branching system (Mukouyama et al., 2002, Mukouyama et al., 2005 and Li et al., 2013) and the mouse sympathetic axon/blood vessel (Honma et al., 2002 and Makita et al., 2008). Understanding how highly stereotyped neurovascular structure is formed to facilitate organ-specific functions will provide insights into the homeostasis and pathogenesis of medical disorders that involve both nerves and vessels. Plxnd1flox/flox mice ( Kim et al., 2011), Nestin-Cre mice ( Tronche et al.