Aberrant neovascularisation contributes to diseases such as cancer, blindness and atherosclerosis and is the consequence of inappropriate angiogenic signalling. While many regulators of pathogenic angiogenesis have been identified, our understanding of this process is incomplete. Here we explored the transcriptome of retinal microvessels isolated from mouse models of retinal disease that exhibit vascular pathology and uncovered an up-regulated gene, leucine-rich alpha-2-glycoprotein-1 (Lrg1), of previously unknown function. We show that in the presence of TGFβ1, LRG1 is mitogenic to endothelial cells and promotes angiogenesis. Mice lacking Lrg1 develop a mild retinal vascular phenotype but exhibit a significant reduction in pathological ocular angiogenesis. LRG1 binds directly to the TGFβ accessory receptor endoglin which, in the presence of TGFβ1, results in promotion of the pro-angiogenic Smad1/5/8 signalling pathway. LRG1 antibody blockade inhibits this switch and attenuates angiogenesis. These studies reveal a novel regulator of angiogenesis that mediates its effect through modulating TGFβ signalling.

Neuregulin switches oligodendrocytes between two modes of myelination: from a neuronal activity–independent mode to a myelin-increasing, neuronal activity–dependent, mechanism that involves glutamate release and NMDA receptor activation.

The concept of adaptive myelination—myelin plasticity regulated by activity—is an important advance for the field. What signals set up the adaptable pattern in the first place? Here we review work that demonstrates an intrinsic pathway within oligodendrocytes requiring only an axon‐shaped substrate to generate multilayered and compacted myelin sheaths of a physiological length. Based on this, we discuss a model we proposed in 2015 which argues that myelination has two phases—intrinsic and then adaptive—which together generate “smart wiring,” in which active axons become more myelinated. This model explains why prior studies have failed to identify a signal necessary for central nervous system myelination and argues that myelination, like synapses, might contribute to learning by the activity‐dependent modification of an initially hard‐wired pattern. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 78: 68–79, 2018