David’s impact also extended to the culture at the MNI. His warm, easygoing, and informal style, underscored by his typical attire of a white shirt and blue jeans, resonated with all; he could often be found in the halls immersed in an animated conversation with security staff, housekeepers, and graduate students. Despite the demands of being Director, Dave sustained a vigorous research program. He and his collaborators demonstrated that cultured neurons readily formed presynaptic structures on synthetic beads coated with adhesive peptides (Lucido et al., 2009), opening new approaches for investigations of synaptogenesis.

An interesting twist Veliparib on this story is that these synapses are active and therefore suggest a potential mechanism to link neuronal signals to synthetic targets for the development of brain-machine interfaces. In another recent paper, Dave’s laboratory discovered a new role for nonprocessed Metformin procadherin molecules in the release of cancer cells from their substrates (Maret et al., 2010), raising prospects of novel therapeutic strategies, focused on cadherin

processing, to limit tumor cell invasion and metastasis. As these studies make clear, David had a wide ranging intellectual curiosity, with broad and varied scientific interests. He sought to look at scientific problems from a fresh vantage, ready to tilt against prevailing orthodoxy as necessary. He made additional contributions to investigations of the axon-glial junction (Dhaunchak et al., 2010 and Pedraza Sorafenib order et al., 2001) and the evolutionary origins of myelin. In collaboration with Boris Zalc, bolstered by field trips to the Muséum national

d’Histoire Naturelle (Paris), they inferred, based on the size of foramen in skulls of fossilized Paleozoic vertebrate fish, that myelin arose some 450 million years ago in placoderms, the first hinge-jawed fish (Zalc and Colman, 2000 and Zalc et al., 2008). In related studies, he collaborated with Dan Harline to examine the nature of the rapid, saltatory conduction in copepods as an example of convergent evolution (Hartline and Colman, 2007). He recently became interested in the poorly understood mechanism(s) by which the myelinating glial cell establishes the multilamellar compact myelin sheath around axons: one of the most striking structures in all of biology. The conventional view has been that the entire inner turn of the myelin sheath moves circumferentially around the axon. Based on a review of older EM studies and staining of markers at the axon-glial interface (Pedraza et al., 2009), David developed a provocative but still to be tested model that the glial cell initially spirals around the axon at each of its ends (akin to a chinese yo-yo, which he would bring to lectures to illustrate the point) and only later fills in the remainder of the glial membrane. Dave was an excellent communicator, which greatly enriched his science and aided his success as advocate and educator.