Abstract:
:Developing neurons of the peripheral nervous system reach their targets via cues that support directional growth, a process known as axon guidance. In investigating how sympathetic axons reach the heart in mice, we discovered that a combination of guidance cues are employed in sequence to refine axon outgrowth, a process we term second-order guidance. Specifically, endothelin-1 induces sympathetic neurons expressing the receptor Ednra to project to the vena cavae leading to the heart. Endothelin signaling in turn induces expression of the repulsive receptor Plexin-A4, via induction of the transcription factor MEF2C. In the absence of endothelin or plexin signaling, sympathetic neurons misproject to incorrect competing vascular trajectories (the dorsal aorta and intercostal arteries). The same anatomical and physiological consequences occur in Ednra+/-; Plxna4+/- double heterozygotes, genetically confirming functional interaction. Second-order axon guidance therefore multiplexes a smaller number of guidance cues in sequential fashion, allowing precise refinement of axon trajectories.
journal_name
Elifejournal_title
eLifeauthors
Poltavski DM,Colombier P,Hu J,Duron A,Black BL,Makita Tdoi
10.7554/eLife.42528subject
Has Abstractpub_date
2019-02-08 00:00:00issn
2050-084Xpii
42528journal_volume
8pub_type
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