PUBLICATION

Elmo1 function, linked to Rac1 activity, regulates peripheral neuronal numbers and myelination in zebrafish

Authors
Mikdache, A., Fontenas, L., Albadri, S., Revenu, C., Loisel-Duwattez, J., Lesport, E., Degerny, C., Del Bene, F., Tawk, M.
ID
ZDB-PUB-190605-10
Date
2019
Source
Cellular and molecular life sciences : CMLS   77(1): 161-177 (Journal)
Registered Authors
Albadri, Shahad, Del Bene, Filippo, Fontenas, Laura, Revenu, Celine, Tawk, Marcel
Keywords
Apoptosis, Dock1, Elmo1, Myelin, PLLg, PLLn, Rac1, Schwann cells, Zebrafish
MeSH Terms
  • Animals
  • Apoptosis
  • Axons/metabolism
  • Axons/ultrastructure
  • Cell Movement
  • Myelin Sheath/metabolism*
  • Neurogenesis*
  • Neurons/cytology*
  • Neurons/metabolism
  • Neurons/ultrastructure
  • Peripheral Nerves/growth & development
  • Peripheral Nerves/ultrastructure
  • Schwann Cells/cytology
  • Schwann Cells/metabolism
  • Schwann Cells/ultrastructure
  • Zebrafish/growth & development*
  • Zebrafish Proteins/metabolism*
  • rac1 GTP-Binding Protein/metabolism*
PubMed
31161284 Full text @ Cell. Mol. Life Sci.
Abstract
Peripheral nervous system development involves a tight coordination of neuronal birth and death and a substantial remodelling of the myelinating glia cytoskeleton to achieve myelin wrapping of its projecting axons. However, how these processes are coordinated through time is still not understood. We have identified engulfment and cell motility 1, Elmo1, as a novel component that regulates (i) neuronal numbers within the Posterior Lateral Line ganglion and (ii) radial sorting of axons by Schwann cells (SC) and myelination in the PLL system in zebrafish. Our results show that neuronal and myelination defects observed in elmo1 mutant are rescued through small GTPase Rac1 activation. Inhibiting macrophage development leads to a decrease in neuronal numbers, while peripheral myelination is intact. However, elmo1 mutants do not show defective macrophage activity, suggesting a role for Elmo1 in PLLg neuronal development and SC myelination independent of macrophages. Forcing early Elmo1 and Rac1 expression specifically within SCs rescues elmo1-/- myelination defects, highlighting an autonomous role for Elmo1 and Rac1 in radial sorting of axons by SCs and myelination. This uncovers a previously unknown function of Elmo1 that regulates fundamental aspects of PNS development.
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