A conserved axon type hierarchy governing peripheral nerve assembly

Liang Wang,Dario Bonanomi,Lukas Cyganek,Samuel L Pfaff,Christiane Nüsslein-Volhard,Alessandro Mongera,Till Marquardt

doi:10.1242/dev.106211

Abstract

In gnathostome vertebrates, including fish, birds and mammals, peripheral nerves link nervous system, body and immediate environment by integrating efferent pathways controlling movement apparatus or organ function and afferent pathways underlying somatosensation. Several lines of evidence suggest that peripheral nerve assembly involves instructive interactions between efferent and afferent axon types, but conflicting findings challenge this view. Using genetic modeling in zebrafish, chick and mouse we uncover here a conserved hierarchy of axon type-dependent extension and selective fasciculation events that govern peripheral nerve assembly, which recapitulates the successive phylogenetic emergence of peripheral axon types and circuits in the vertebrate lineage.

Highlights

Nervous system evolution seems to have frequently proceeded via the use of pre-existing axon pathways, rather than through de novo formation of nerve tracts, to accommodate novel features within extant circuits (Katz, 1983; Katz et al, 1983)
Conserved reliance of sensory axon extension on pioneer motor axons To explore the interactions between primary somatosensory afferent axons (SAs) and motor efferent axons (MEs) we first systematically investigated the relationships between molecularly identified peripheral axon types in three different vertebrate species: zebrafish (D. rerio: Fig. 1A), chick (G. gallus domesticus: Fig. 1J) and mouse (M. musculus: Fig. 1S)
In anamniotes, including zebrafish, the first emerging sensory-motor circuits are dedicated to simple larval escape reflexes that are mediated by an early central nervous system (CNS) neuron population, Rohon Beard cells (RBs), which feed primary sensory inputs from dermis to motor neurons controlling trunk musculature (Spitzer, 1984)

Summary

Introduction

Nervous system evolution seems to have frequently proceeded via the use of pre-existing axon pathways, rather than through de novo formation of nerve tracts, to accommodate novel features within extant circuits (Katz, 1983; Katz et al, 1983). The segmental organization of the vertebrate body axis, for example, places constraints on peripheral axon growth that force primary somatosensory axons (SAs) to extend through peripheral nerve tracts that are occupied by more ancestral motor efferent axons (MEs) (Bonanomi and Pfaff, 2010; Butler and Hodos, 2005). Such co-confinement to narrow substrate corridors may effectively foster interactions between axons that extend from phylogenetically newer or older neuron types, and accelerate their incorporation into common functional assemblies. Genetic manipulations that completely blocked ME extension resulted in randomized extension of SAs along dorsal or ventral trajectories, whereas ME-restricted elimination of the EphA receptor tyrosine kinases EphA3 and EphA4 triggered selective dorsal-to-ventral misrouting of SAs (Wang et al, 2011; Wang and Marquardt, 2013)

Methods

Results

Conclusion