Abstract
The sympathetic nervous system is essential for maintaining mammalian homeostasis. How this intricately connected network, composed of preganglionic neurons that reside in the spinal cord and post-ganglionic neurons that comprise a chain of vertebral sympathetic ganglia, arises developmentally is incompletely understood. This problem is especially complex given the vertebral chain of sympathetic ganglia derive secondarily from the dorsal migration of ‘primary' sympathetic ganglia that are initially located several hundred microns ventrally from their future pre-synaptic partners. Here we report that the dorsal migration of discrete ganglia is not a simple migration of individual cells but a much more carefully choreographed process that is mediated by extensive interactions of pre-and post-ganglionic neurons. Dorsal migration does not occur in the absence of contact with preganglionic axons, and this is mediated by BDNF/TrkB signalling. Thus BDNF released by preganglionic axons acts chemotactically on TrkB-positive sympathetic neurons, to pattern the developing peripheral nervous system.
Highlights
The sympathetic nervous system is essential for maintaining mammalian homeostasis
On delamination from the neural tube, trunk neural crest cells destined to form the vertebral chain of sympathetic ganglia migrate ventrally to the vicinity of the dorsal aorta where they aggregate and condense to form the primary chain of sympathetic ganglia composed of differentiated sympathetic neurons and precursor cells[1]
Alternative models suggest that multipotent neural crest cells respond dynamically to the microenvironmental signals that are regulated in space and time to direct emerging neural crest cells towards the dorsal aorta, sculpt individual cells into discrete clusters of primary sympathetic ganglia or halt their migration more dorsally to form dorsal root ganglia[8,9,10,11]
Summary
The sympathetic nervous system is essential for maintaining mammalian homeostasis How this intricately connected network, composed of preganglionic neurons that reside in the spinal cord and post-ganglionic neurons that comprise a chain of vertebral sympathetic ganglia, arises developmentally is incompletely understood. The more recent advances in molecular data on signals[12,13,14,15,16,17] that appear to march along with the repeating pattern of discrete ganglia or localize near the incipient primary sympathetic ganglia before the arrival of ventral moving neural crest cells has re-awakened interest in identifying the cellular mechanisms that mediate the multi-step pattern formation of the developing nervous system. There is a critical need for spatio-temporal information about individual and multicellular neural crest cell dynamics during nervous system development and a means to identify and accurately link gene function with local morphological changes in the tissue. Our goal was to understand the multicellular migration dynamics that mediate the primary to permanent sympathetic ganglia formation and probe the role of the preganglionic sympathetic axons that extend from neuronal cell bodies in the spinal cord, during this dorsal migration
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