In the area of basic neurobiology, our laboratory is currently investigating interactions leading to establishment of neuronal arbors with specific morphologies. In particular, we have focused on the mechanisms which receptors and signaling factors use to mediate self- and homologue-avoidance in the process of defining cell arbor boundaries, a phenomenon that is known as tiling and defines the topology of sensory and motor fields
Our studies are carried out in the medicinal leech (Hirudo medicinalis, Hirudo verbana), for which we have created genomic and transcriptomic databases and are in the process of annotating the genome. Its nervous system provides a very accessible experimental platform for molecular and cellular studies; we have developed or adapted all the tools required for modulating the expression of specific genes in individual embryonic or adult identified leech neurons (see Figure 1).
We are particularly interested currently in the roles of gap junctions (GJs) in the early differentiation of the central nervous system. We have cloned and characterized the expression patterns of the 21 leech GJ genes (innexins) in the Hirudo genome; 14 or 15 are expressed in central and/or peripheral neurons in the embryo and adult (see Figure 2). In one set of studies, we have shown that innexins can not only form gap junctions but can also form functional hemi-channels that can provide intracellular and intercellular signaling via small molecules, such as ATP.
Individual identified central neurons express different subsets of innexin genes, which we have proposed as the determining factor in the specificity of electrically-coupled networks. In one set of studies, we also demonstrated that expression of certain pan-neuronal innexins is necessary for the formation of of gap junctions, while ectopic expression of certain other innexins is sufficient for the formation of novel coupled networks in the CNS.
A major effort at present is to explore, using null and functionally-deficient mutations, the role of innexins in interactions between segmental homologs that result in the retraction of some neuronal projections and the maintenance of others (see Figure 3).
In a very different area of research, we are also involved in a multidisciplinary project at the boundary of Neuroscience and Architecture. This project brings together human brain activity monitoring using portable high-definition EEG with cutting-edge Virtual Reality facilities on campus to assay human responses to the built environment, in particular, as the subjects attempt to navigate through a complex building. This project has exciting practical ramifications, for example, in providing evidence for the design of better healthcare and educational facilities, as well as testing therapies for improving the status of humans with neural impairment conditions.
Eduardo Macagno received his Ph.D. from Columbia University in 1968. He was on the faculty of Columbia from 1973 to 2000. From 1993 to 2000 he served as Associate Vice President for Research and Graduate Education and Dean of the Graduate School of Arts and Sciences at Columbia. He joined the faculty of the Division of Biological Sciences as Founding Dean in 2001. He is the Editor of Developmental Neurobiology and the President of the Academy of Neuroscience for Architecture. He also serves on review committees for the Life Sciences Research Foundation and the W. M. Keck Foundation.