2 RECEPTOR TYROSINE PHOSPHATASES OF THE LAR FAMILY ARE EXPRESSED IN THE DEVELOPING LEECH BY SPECIFIC CENTRAL NEURONS AS WELL AS SELECT PERIPHERAL NEURONS, MUSCLES, AND OTHER CELLS

Receptor protein tyrosine phosphatases (rPTPs) are thought to play a c rucial role in neuronal development, particularly in pathfinding by gr owing processes. We have cloned and sequenced two Hirudo medicinalis r PTPs that are homologous to the Drosophila and vertebrate rPTPs of the Leukocyte common antigen-related (LAR) subfamily. These Hirudo rPTPs, HmLAR1 and HmLAR2, are products of different, homologous genes, both containing two tandem intracellular phosphatase domains and ectodomain s with three tandem Ig domains and different numbers of tandem fibrone ctin type III (FIII) domains. They are expressed in distinct patterns during embryogenesis. HmLAR1 mRNA is expressed by a subset of central and peripheral neurons and by several peripheral muscular structures, whereas HmLAR2 mRNA is expressed by a different subset of central neur ons and by the peripheral, neuron-like Comb cells. HmLAR1 and HmLAR2 p roteins are located on the neurites of central neurons. In addition, H mLAR2 is expressed on the cell body, processes, and growth cones of th e Comb cells. Because of their CAM-like ectodomains and homology to pr oteins known to be involved in pathfinding and because they are expres sed by different subsets of neurons, we hypothesize that HmLAR1 and Hm LAR2 participate in navigational decisions that distinguish the sets o f neurons that express them. Furthermore, we hypothesize that HmLAR2 i s also involved in setting up the highly regular array of parallel pro cesses established by the Comb cells. Lastly, we propose that the HmLA R1 ectodomain on peripheral muscle cells plays a role in target recogn ition via interactions with neuronal receptors, which might include Hm LAR1 or HmLAR2.