The long-range goal of this work is to understand certain fundamental mechanisms of development, particularly regarding neurogenesis, differentiation and selective synapse formation. This goal is addressed by studying how individual regions of the central nervous system, and nerve cells within those regions, become morphologically and physiologically differentiated from one another during development in order to perform specialized functions. The segmented nervous system of the medicinal leech was chosen for these experiments because of its great simplicity, the possibility of studying individual identified neurons repeatedly, and the ready accessibility of embryonic and postembryonic stages to experimental manipulation. There are two parts to this project. The first part concerns the very basic question of how the generation of central neurons may be regulated by peripheral organs. It comprises the study of an interaction between the male genitalia and the two central ganglia that innervate it. This interaction is mediated by an inductive signal that triggers the birth and differentiation of a special population of neurons in these ganglia. The experiments proposed are designed to yield answers to the questions (1) when exactly does the interaction take place?, (2) is the time of interaction defined by the nervous system or by the target tissue?, and (3) which cells are the source of the inductive signal, which carry it to the central nervous system, and which cells respond to the signal? Identification of the cellular elements involved in this interaction is a necessary prerequisite for the future exploration of the molecular mechanisms of this interaction. The second part of this project addresses another basic question: how selectivity in the formation of synaptic connections is achieved. It consists of a comprehensive examination of the interactions between an identified motor neuron and peripheral tissues that result in the formation of neuromuscular junctions with the neuron's target, the male genitalia. These experiments are carried out, in a complementary manner, both in the animal and in isolated cells in culture. A multi-faceted approach, involving embryological perturbations and electrophysiological, anatomical and immunocytological techniques, will be employed in this project. Further detailed study of these fundamental problems in the simple nervous system of the medicinal leech will provide valuable insights applicable to the study of both normal and abnormal development of more complex systems.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Other Domestic Higher Education
New York
United States
Zip Code
Wolszon, L R; Passani, M B; Macagno, E R (1995) Interactions during a critical period inhibit bilateral projections in embryonic neurons. J Neurosci 15:1506-15
Wolszon, L R; Rehder, V; Kater, S B et al. (1994) Calcium wave fronts that cross gap junctions may signal neuronal death during development. J Neurosci 14:3437-48
Wolszon, L R; Gao, W Q; Passani, M B et al. (1994) Growth cone ""collapse"" in vivo: are inhibitory interactions mediated by gap junctions? J Neurosci 14:999-1010
Camhi, J M; Macagno, E (1991) Using fluorescence photoablation to study the regeneration of singly cut leech axons. J Neurobiol 22:116-29
Stewart, R R; Gao, W Q; Macagno, E R (1991) Segmental differentiation in the leech central nervous system: proposed segmental homologs of the heart accessory neurons. J Comp Neurol 313:431-40
Macagno, E R; Gao, W Q; Baptista, C A et al. (1990) Competition or inhibition? Developmental strategies in the establishment of peripheral projections by leech neurons. J Neurobiol 21:107-19
Peinado, A; Zipser, B; Macagno, E R (1990) Segregation of afferent projections in the central nervous system of the leech Hirudo medicinalis. J Comp Neurol 301:232-42
Baptista, C A; Macagno, E R (1988) The role of the sexual organs in the generation of postembryonic neurons in the leech Hirudo medicinalis. J Neurobiol 19:707-26
Gao, W Q; Macagno, E R (1988) Axon extension and retraction by leech neurons: severing early projections to peripheral targets prevents normal retraction of other projections. Neuron 1:269-77
Baptista, C A; Macagno, E R (1988) Modulation of the pattern of axonal projections of a leech motor neuron by ablation or transplantation of its target. Neuron 1:949-62

Showing the most recent 10 out of 19 publications