Dual topologies of myotomal collagen XV and Tenascin C act in concert to guide and shape developing motor axons

Laurie Nemoz-Billet, Martial Balland, Laurent Gilquin, Benjamin Gillet, Isabelle Stévant, Emilie Guillon, Sandrine Hughes, Gilles Carpentier, Elisabeth Vaganay, Frédéric Sohm, Vladimir Misiak, Mary Julieth Gonzalez-Melo, Manuel Koch, Yad Ghavi-Helm, Sandrine Bretaud, Florence Ruggiero

Research output: Contribution to journalArticlepeer-review


During development, motor axons are guided toward muscle target by various extrinsic cues including extracellular matrix (ECM) proteins whose identities and cellular source remain poorly characterized. Here, using single-cell RNAseq of sorted GFP+ cells from smyhc1:gfp-injected zebrafish embryos, we unravel the slow muscle progenitors (SMP) pseudotemporal trajectory at the single-cell level and show that differentiating SMPs are a major source of ECM proteins. The SMP core-matrisome was characterized and computationally predicted to form a basement membrane–like structure tailored for motor axon guidance, including basement membrane–associated ECM proteins, as collagen XV-B, one of the earliest core-matrisome gene transcribed in differentiating SMPs and the glycoprotein Tenascin C. To investigate how contact-mediated guidance cues are organized along the motor path to exert their function in vivo, we used microscopy-based methods to analyze and quantify motor axon navigation in tnc and col15a1b knock-out fish. We show that motor axon shape and growth rely on the timely expression of the attractive cue Collagen XV-B that locally provides axons with a permissive soft microenvironment and separately organizes the repulsive cue Tenascin C into a unique functional dual topology. Importantly, bioprinted micropatterns that mimic this in vivo ECM topology were sufficient to drive directional motor axon growth. Our study offers evidence that not only the composition of ECM cues but their topology critically influences motor axon navigation in vertebrates with potential applications in regenerative medicine for peripheral nerve injury as regenerating nerves follow their original path.

Original languageEnglish
Article numbere2314588121
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - 26 Mar 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2024 the Author(s).


  • extracellular matrix
  • motor axon pathfinding
  • muscle progenitors
  • scRNA seq
  • zebrafish


Dive into the research topics of 'Dual topologies of myotomal collagen XV and Tenascin C act in concert to guide and shape developing motor axons'. Together they form a unique fingerprint.

Cite this