One of the fundamental yet largely unanswered questions about the development of the nervous system is how one region becomes morphologically and functionally different from another during neurogenesis. The long-range goal of this project is to discover the mechanisms that give rise to this regional specialization in the leech nervous system. Regional specialization could derive from factors intrinsic to the neuronal precursors for each region, or from factors introduced by interactions with other neural or non-neural tissues. We have chosen to carry out our observations and experiments on leech segmental ganglia because of their relative simplicity and accessibility to experimental manipulation. We have previously determined that the ganglia in body segments five and six, which innervate the sexual organs, contain a few hundred more neurons than adjacent ganglia. The first objective of this project is to characterize in detail these extra neurons, both in development and in the adult. This will entail describing when these neurons arise, what their birthdates, are, which cells are their precursors, when they innervate the sexual organs, and what their functions are. We will do this by using a variety of techniques, including computer-aided techniques to do cell counts and cell reconstructions, [3H]-thymidine labeling to obtain birthdates and to identify precursors, and cell recording, dye injection and histology to determine their functions. In addition we will use monoclonal antibodies to identify particular cells during development. On the basis of the detailed information we obtain, we will refine our hypotheses about the mechanisms that underlie segmental specialization in the leech. The second objective of this project is to begin testing these hypotheses experimentally by performing various manipulations on the developing ganlia, such as isolating the ganglia in the animal by cutting connecting nerves, placing ganglia in culture with or without other tissues, transplanting ganglia into hosts of different ages, and removing individual ganglia. The effects of these manipulations will be studied with the techniques mentioned above. Detailed study of segmental specialization in the leech, with its relatively simple nervous system, can yield valuable insights applicable to studies of this fundamental problem in more complex organisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020336-02
Application #
3400653
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-12-01
Project End
1990-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Graduate Schools
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
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

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