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The development of a patterned vasculature is essential for normal organogenesis. We found that signaling by semaphorin 3E (Sema3E) and its receptor plexin-D1 controls endothelial cell positioning and the patterning of the developing vasculature in the mouse. Sema3E is highly expressed in developing somites, where it acts as a repulsive cue for(More)
Neuropilin-1 (Npn-1) is a receptor that binds multiple ligands from structurally distinct families, including secreted semaphorins (Sema) and vascular endothelial growth factors (VEGF). We generated npn-1 knockin mice, which express an altered ligand binding site variant of Npn-1, and npn-1 conditional null mice to establish the cell-type- and ligand(More)
Neuropilin-1 (Npn-1) is a receptor for both semaphorin 3A (Sema3A) and vascular endothelial growth factor 165 (VEGF(165)). To understand the role Npn-1 plays as a receptor for these structurally and functionally unrelated ligands, we set out to identify structural features of Npn-1 that confer binding to Sema3A or VEGF(165). We constructed Npn-1 variants(More)
Developing neurons accurately position their somata within the neural tube to make contact with appropriate neighbors and project axons to their preferred targets. Taking advantage of a collection of genetically engineered mouse mutants, we now demonstrate that the behavior of somata and axons of the facial nerve is regulated independently by two secreted(More)
The central nervous system (CNS) requires a tightly controlled environment free of toxins and pathogens to provide the proper chemical composition for neural function. This environment is maintained by the 'blood-brain barrier' (BBB), which is composed of blood vessels whose endothelial cells display specialized tight junctions and extremely low rates of(More)
Neuropilins, secreted semaphorin coreceptors, are expressed in discrete populations of spinal motor neurons, suggesting they provide critical guidance information for the establishment of functional motor circuitry. We show here that motor axon growth and guidance are impaired in the absence of Sema3A-Npn-1 signaling. Motor axons enter the limb(More)
Neurovascular interactions are essential for proper brain function. While the effect of neural activity on cerebral blood flow has been extensively studied, whether or not neural activity influences vascular patterning remains elusive. Here, we demonstrate that neural activity promotes the formation of vascular networks in the early postnatal mouse barrel(More)
In developing limb skin, peripheral nerves are required for arterial differentiation, and guide the pattern of arterial branching. In vitro experiments suggest that nerve-derived VEGF may be important for arteriogenesis, but its role in vivo remains unclear. Using a series of nerve-specific Cre lines, we show that VEGF derived from sensory neurons,(More)
The nervous and vascular systems are both exquisitely branched and complicated systems and their proper development requires careful guidance of nerves and vessels. The recent realization that common ligand-receptor pairs are used in guiding the patterning of both systems has prompted the question of whether similar signaling pathways are used in both(More)
Pioneer axons from the cingulate cortex initiate corpus callosum (CC) development, yet nothing is known about the molecules that regulate their guidance. We demonstrate that neuropilin 1 (Npn1) plays an integral role in the development of the CC. Npn1 is localized to axons of cingulate neurons as they cross the midline, and multiple class 3 semaphorins(More)