Met is required for oligodendrocyte progenitor cell migration inDanio rerio

Abstract

During vertebrate central nervous system development, most oligodendrocyte progenitor cells (OPCs) are specified in the ventral spinal cord and must migrate throughout the neural tube until they become evenly distributed, occupying non-overlapping domains. While this process of developmental OPC migration is well characterized, the nature of the molecular mediators that govern it remain largely unknown. Here, using zebrafish as a model, we demonstrate that Met signaling is required for initial developmental migration of OPCs, and, using cell-specific knock-down of Met signaling, show that Met acts cell-autonomously in OPCs. Taken together, these findings demonstrate in vivo, the role of Met signaling in OPC migration and provide new insight into how OPC migration is regulated during development.

Glial Patchwork: Oligodendrocyte Progenitor Cells and Astrocytes Blanket the Central Nervous System

“…Following the specification, OPCs rapidly disperse throughout the CNS until they occupy distinct, non-overlapping territories (Cai et al, 2005 ; Kirby et al, 2006 ; De Biase et al, 2017 ; Ravanelli et al, 2018 ). This process of OPC dispersal is termed developmental OPC tiling and is comprised of three main components: migration, proliferation, and CMR ( Figures 1A–C ; Kirby et al, 2006 ; Cameron and Rao, 2010 ; Hughes et al, 2013 ; Ali et al, 2021 ). In the literature, most investigations of OPC development focus on either OPC specification or differentiation into oligodendrocytes, the myelinating cells of the CNS (Richardson et al, 2006 ; Bergles and Richardson, 2015 ; Kearns et al, 2015 ; Crawford et al, 2016 ; Nishiyama et al, 2016 ; Chapman et al, 2018 ; Ravanelli et al, 2018 ; Hayashi and Suzuki, 2019 ; Kuhn et al, 2019 ; Perlman et al, 2020 ).…”

“…However, mouse mutants for Met are embryonic lethal. Recently, we utilized zebrafish as a vertebrate model and demonstrated that Met signaling is required for initial OPC migration (Ali et al, 2021 ). Utilizing both CRISPR/Cas9-mediated met mutagenesis and dominant negative Met transgenic fish, we demonstrated that loss of Met signaling significantly reduced the number of migrating OPCs during developmental tiling.…”

“…Utilizing both CRISPR/Cas9-mediated met mutagenesis and dominant negative Met transgenic fish, we demonstrated that loss of Met signaling significantly reduced the number of migrating OPCs during developmental tiling. However, a small population of OPCs was still able to migrate in the absence of Met signaling, demonstrating that a single cue is not responsible for OPC migration and that the OPC population is heterogeneous in its response to distinct cues (Ali et al, 2021 ). This study demonstrates the necessity of investigating glial dynamics in vivo and the importance of using multiple animal models.…”

“…For example, CXCL1 and CXCL12 have opposite effects on OPC migration but are both purported to stimulate OPC proliferation (Watson et al, 2020 ). Additionally, the Met signaling pathway promotes OPC proliferation as well as migration (Ohya et al, 2007 ; Ali et al, 2021 ). The C-x-c motif ligands were investigated in the developing cortex, while the Met signaling pathway was investigated in the spinal cord, which indicates that regional differences in OPC populations could regulate which mitogens influence OPC proliferation during developmental tiling.…”

Unique advantages of zebrafish larvae as a model for spinal cord regeneration

“…The identity and position of differentiated neuronal subtypes is largely established by 3 dpf (Seredick et al, 2012 ; Reimer et al, 2013 ; Lien et al, 2016 ; Ohnmacht et al, 2016 ; Andrzejczuk et al, 2018 ; England et al, 2020 ), and by 4 dpf these neurons are assembled into functional circuits required for the transition to a mature swimming pattern, increased locomotion, and the emergence of foraging behavior (Buss and Drapeau, 2001 ; Borla et al, 2002 ; Kokel et al, 2010 ; Menelaou and McLean, 2012 ; Kroll et al, 2021 ; Pallucchi et al, 2022 ). Ependymal radial glia (ERG), the resident neural progenitor cells of the zebrafish spinal cord (Briona and Dorsky, 2014a ; Hui et al, 2015 ), begin to establish characteristic marker expression and morphology at 2 dpf (Kim et al, 2008 ; Briona and Dorsky, 2014a ; Matsuoka et al, 2016 ), and subpopulations of ERG have become fate-restricted by 3 dpf (Ali et al, 2021 ). Oligodendrocytes, one of the latest born spinal cord cell types, are generated and begin myelinating axon tracts by 2.5 dpf (Park et al, 2002 ; Kirby et al, 2006 ; Ali et al, 2021 ).…”