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.
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