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Publication

Venous endothelin modulates responsiveness of cardiac sympathetic axons to arterial semaphorin.

eLife | 2019

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.

Pubmed ID: 30735130 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

ATCC (RRID:SCR_001672)

Antibodies used in this publication

Associated grants

Agency: NINDS NIH HHS, United States
Id: K99 NS062901
Agency: NINDS NIH HHS, United States
Id: NS083265
Agency: NHLBI NIH HHS, United States
Id: HL064658
Agency: NINDS NIH HHS, United States
Id: R01 NS083265
Agency: NINDS NIH HHS, United States
Id: NS062901
Agency: NHLBI NIH HHS, United States
Id: R01 HL064658
Agency: NHLBI NIH HHS, United States
Id: R01 HL136182
Agency: NHLBI NIH HHS, United States
Id: HL136182
Agency: NINDS NIH HHS, United States
Id: R00 NS062901

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This is a list of tools and resources that we have found mentioned in this publication.

ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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SEMA6B Antibody (G-7) (antibody)

RRID:AB_2783522

This monoclonal targets SEMA6B

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Anti-Semaphorin 3F antibody (antibody)

RRID:AB_2783521

This polyclonal targets Anti-Semaphorin 3F

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Rabbit Anti-HCN4 Polyclonal Antibody, Unconjugated (antibody)

RRID:AB_1861080

This polyclonal targets HCN4

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SYP (D-4) (antibody)

RRID:AB_628311

This monoclonal targets SYP

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Anti-Tyrosine Hydroxylase Antibody (antibody)

RRID:AB_90755

This polyclonal targets Tyrosine Hydroxylase

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Anti-Semaphorin 3A antibody (antibody)

RRID:AB_447408

This polyclonal targets Semaphorin 3A

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Plexin A4 Antibody (antibody)

RRID:AB_11013411

This unknown targets Plexin A4

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COS-7 (cell line)

RRID:CVCL_0224

Cell line COS-7 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)

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CASAVA (software resource)

RRID:SCR_001802

Software package that creates genomic builds, calls SNPs, detects indels, and counts reads from data generated from one or more sequencing runs. In addition, CASAVA automatically generates a range of statistics, such as mean depth and percentage chromosome coverage, to enable comparison with previous builds or other samples. CASAVA analyzes sequencing reads in three stages: * FASTQ file generation and demultiplexing * Alignment to a reference genome * Variant detection and counting

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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ADInstruments - Data Acquisition Systems for Life Science (material resource)

RRID:SCR_001620

THIS RESOURCE IS NO LONGER IN SERVICE, documented on May 19, 2018; A provider of computer-based data acquisition and analysis systems for life science. Products enable users to record and analyze life science data quickly and efficiently. ADInstruments product range is based on the PowerLab data acquisition system with LabChart software. The PowerLab system (also MacLab) is used in universities, hospitals, research institutes, pharmaceutical companies, contract research organizations and other private industry research sectors.

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