Multiple strategies for directed growth cone extension and navigation of peripheral neurons

Abstract

Leeches have a diverse constellation of peripheral neural elements that are challenged to extend growth cones in highly specific ways in a constantly changing embryonic environment. Two major systems are reviewed here. In one, peripheral afferents extend growth cones toward the central nervous system (CNS), forming common pathways, and then segregate into particular tracts within the CNS. A majority of these afferents depend on CNS-derived guidance cues and projections from the CNS to guide their way. However, not all of the nerves are established this way and at least one of the peripheral nerves is likely to be pioneered by sensillar sensory afferents. The distribution of particular antigens (such as the lan3-2 antigen) suggests the identity of molecules involved in homophilic adhesion along common pathways, whereas others (such as the lan4-2 and 3-6 antigens) are candidates for mediating specific pathway choices. In the second system, the myo-organizing Comb cell (C cell) projects multiple growth cones simultaneously along oblique trajectories not influenced by segmental or midline boundaries. Its parallel growth cones exhibit space-filling as well as directional growth and are guided by local cues to extend in discrete phases that are coordinated with the development of the environment. Both systems exhibit highly directed outgrowth orchestrated by a hierarchy of cues, establish patterns of neurites used to direct later migrating cells, and seem to be regulated temporally and spatially by interactions with the embryonic environment. These systems illustrate the strengths of examining neural development in vivo across several levels of analysis.

Calsensin: a novel calcium-binding protein expressed in a subset of peripheral leech neurons fasciculating in a single axon tract.

“…The molecular features of calsensin and its association with the 200,000 Mr protein are consistent with the hypothesis that it may participate in a protein complex mediating calcium-dependent signal transduction events in growth cones and axons (Johansen et al, 1994;Jellies and Johansen, 1995). It has become increasingly clear that the functions of many molecules involved in cell adhesion and fascicle formation, apart from being effected by their extracellular interactions, are also to a great extent determined by their associations with cytoplasmic proteins and cytoskeletal structures, associations which are often regulated by signal transduction processes and second messenger pathways (Schuch et al, 1989;Atashi et al, 1992;Hynes, 1992;Gumbiner, 1993).…”

Molecular identification and expression of the NMDA receptor NR1 subunit in the leech

“…RNAi) that will help elucidate the role of NMDARs in a number of physiological processes including learning and memory. In addition, leech genera, such as Hirudo and Helobdella, have been used as model systems for studying the cellular basis of neurodevelopment (Levine and Macagno 1990;Jellies and Johansen 1995;Kristan et al 2000;Weisblat 2007). Given that the NMDAR is critical for neurodevelopment in vertebrates (Dumas 2005), genetic manipulation of NMDARs in the leech may reveal important details about the development of neural circuits.…”

Differential expression of the EF-hand calcium-binding protein calsensin in the central nervous system of hirudinid leeches

“…Each of the 21 iterated segmental ganglia contains only approximately 400 neurons (Macagno 1980), many of which are identified and have known physiological roles (Muller et al 1981). In addition, the peripheral nervous system (PNS) is well characterized, and both PNS and central nervous system (CNS) development can be analyzed embryologically by a variety of techniques (Jellies and Johansen 1995). The formation of the nervous system proceeds in a rostrocaudal sequence, generally, with each posterior segment being 2.5 h later in development than its immediate anterior segment .…”