Semaphorins (SEMAs) and their Plexin (PLXN) receptors are central regulators of metazoan cellular... more Semaphorins (SEMAs) and their Plexin (PLXN) receptors are central regulators of metazoan cellular communication. SEMA-PLXND1 signaling plays important roles in cardiovascular, nervous, and immune system development, and cancer biology. However, little is known about the molecular mechanisms that modulate SEMA-PLXND1 signaling. As PLXND1 associates with GIPC family endocytic adaptors, we evaluated the requirement for the molecular determinants of their association and PLXND1’s vascular role. Zebrafish that endogenously express a Plxnd1 receptor with a predicted impairment in GIPC binding exhibit low penetrance angiogenesis deficits and antiangiogenic drug hypersensitivity. Moreover, gipc mutant fish show angiogenic impairments that are ameliorated by reducing Plxnd1 signaling. Finally, GIPC depletion potentiates SEMA-PLXND1 signaling in cultured endothelial cells. These findings expand the vascular roles of GIPCs beyond those of the Vascular Endothelial Growth Factor (VEGF)-dependent...
The cerebral vasculature provides the massive blood supply that the brain needs to grow and survi... more The cerebral vasculature provides the massive blood supply that the brain needs to grow and survive. By acquiring distinctive cellular and molecular characteristics it becomes the Blood Brain Barrier (BBB), a selectively permeable and protective interface between the brain and the peripheral circulation that maintains the extra-cellular milieu permissive for neuronal activity. Accordingly, there is great interest in uncovering the mechanisms that modulate the formation and differentiation of the brain vasculature. By performing a forward genetic screen in zebrafish we isolated no food for thought (nft(y72)), a recessive late-lethal mutant that lacks most of the intra-cerebral Central Arteries (CtAs), but not other brain blood vessels. We found that the cerebral vascularization deficit of nft(y72) is caused by an inactivating lesion in reck (reversion-inducing-cysteine-rich protein with Kazal motifs or ST15; Suppressor of Tumorigenicity 15 protein), which encodes a membrane-anchored ...
Semaphorins (SEMAs) and their Plexin (PLXN) receptors are central regulators of metazoan cellular... more Semaphorins (SEMAs) and their Plexin (PLXN) receptors are central regulators of metazoan cellular communication. SEMA-PLXND1 signaling plays important roles in cardiovascular, nervous, and immune system development, and cancer biology. However, little is known about the molecular mechanisms that modulate SEMA-PLXND1 signaling. As PLXND1 associates with GIPC family endocytic adaptors, we evaluated the requirement for the molecular determinants of their association and PLXND1’s vascular role. Zebrafish that endogenously express a Plxnd1 receptor with a predicted impairment in GIPC binding exhibit low penetrance angiogenesis deficits and antiangiogenic drug hypersensitivity. Moreover, gipc mutant fish show angiogenic impairments that are ameliorated by reducing Plxnd1 signaling. Finally, GIPC depletion potentiates SEMA-PLXND1 signaling in cultured endothelial cells. These findings expand the vascular roles of GIPCs beyond those of the Vascular Endothelial Growth Factor (VEGF)-dependent...
The cerebral vasculature provides the massive blood supply that the brain needs to grow and survi... more The cerebral vasculature provides the massive blood supply that the brain needs to grow and survive. By acquiring distinctive cellular and molecular characteristics it becomes the Blood Brain Barrier (BBB), a selectively permeable and protective interface between the brain and the peripheral circulation that maintains the extra-cellular milieu permissive for neuronal activity. Accordingly, there is great interest in uncovering the mechanisms that modulate the formation and differentiation of the brain vasculature. By performing a forward genetic screen in zebrafish we isolated no food for thought (nft(y72)), a recessive late-lethal mutant that lacks most of the intra-cerebral Central Arteries (CtAs), but not other brain blood vessels. We found that the cerebral vascularization deficit of nft(y72) is caused by an inactivating lesion in reck (reversion-inducing-cysteine-rich protein with Kazal motifs or ST15; Suppressor of Tumorigenicity 15 protein), which encodes a membrane-anchored ...
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Papers by carlos narvaez