Eduardo Macagno


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

Figure 1

Figure 1. Pair of Live Medicinal Leech Embryos

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).

Figure 2

Figure 2. Bilateral pair of electrically-coupled central neurons in the medicinal leech

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).

Figure 3

Figure 3. Some pairs of homologous central neurons retract overlapping projections (AP cell; panel A, panel D), while others form GJs and are retained without major overlap (S cell; panel B) or do not form GJs and ignore each other (P cell; panel C). Knockout of a necessary GJ gene, Inx1, leads to the retention of AP interganglionic projections (cf. panels E and F), with continued growth into adjacent segment (panels G and H)

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.


  • The Medicinal Leech Genome Encodes 21 Innexin Genes: Different Combinations Are Expressed by Identified Central Neurons. B. Kandarian, J. Sethi, A.Y. Wu, M.W. Baker, N. Yazdani, E. Kym, A. Sanchez, L. Edsall, T. Gaasterland and E.R. Macagno. Develop Genes Evol 222:29-44 (2012). PMID:22358128
  • Ectopic expression of select innexins in individual central neurons couples them to pre-existing neuronal or glial networks that express the same innexin. C.P. Firme, R.G. Natan, N. Yazdani, E.R. Macagno, M.W. Baker. J Neurosci 32:14265-70 (2012).PMID:23055495
  • Expression of a dominant negative mutant innexin in identified neurons and glial cells reveals selective interactions among gap junctional proteins. N. Yazdani, C.P. Firme 3rd, E.R. Macagno, MW Baker. Dev Neurobiol 1002/dneu.22082. [Epub ahead of print] (2013) PMID:23447124
  • Microscopy Ambient Ionization Top-Down Mass Spectrometry Reveals Developmental Patterning. C.-C. Hsu, N. White, M. Hayashi, E.C. Lin, T. Poon, I. Banerjee, J. Chen, S. Pfaff, E.R. Macagno, P.C. Dorrestein. Proc. Nat. Acad. Sci. USA 110:14855-60 (2013) PMID:23969833
  • Gap Junction-Dependent Homolog Avoidance in the Developing CNS. M.W. Baker, N. Yazdani, E.R. Macagno. J Neurosci 33:16673-83 (2013) PMID:24133270
  • Control of Neuronal Morphology and Connectivity: Emerging Developmental Roles for Gap Junctional Proteins. M.W. Baker, E.R. Macagno. FEBS Letters FEBS Lett 588:1470-9 (2014).