The Shh receptor Boc is important for myelin formation and repair

Abstract

Myelination leads to the formation of myelin sheaths surrounding neuronal axons and is crucial for function, plasticity and repair of the central nervous system (CNS). It relies on the interaction of the axons and the oligodendrocytes: the glial cells producing CNS myelin. Here, we have investigated the role of a crucial component of the Sonic hedgehog (Shh) signalling pathway, the co-receptor Boc, in developmental and repairing myelination. During development, Boc mutant mice display a transient decrease in oligodendroglial cell density together with delayed myelination. Despite recovery of oligodendroglial cells at later stages, adult mutants still exhibit a lower production of myelin basic protein correlated with a significant decrease in the calibre of callosal axons and a reduced amount of the neurofilament NF-M. During myelin repair, the altered OPC differentiation observed in the mutant is reminiscent of the phenotype observed after blockade of Shh signalling. In addition, Boc mutant microglia/macrophages unexpectedly exhibit the apparent inability to transition from a highly to a faintly ramified morphology in vivo. Altogether, these results identify Boc as an important component of myelin formation and repair.

Zebrafish spinal cord oligodendrocyte formation requiresbocfunction

“…Thus, progenitor populations in different regions of the developing nervous system may have a common requirement for Boc function in formation of OPCs from neural progenitors. The developing dorsal forebrain of Boc mutant mice also had fewer differentiating oligodendrocytes and less myelin than wild-type mice, although the ratio of oligodendrocytes to OPCs was similar to that of wild type (Zakaria et al 2019). Thus, in both zebrafish and mice Boc function appears to be required for OPC production and not for oligodendrocyte differentiation.…”

“…Mutant larvae had deficits of both total oligodendrocyte lineage cells and differentiating oligodendrocytes, suggesting that fewer OPCs are formed by neural progenitors in the absence of boc function, resulting in formation of fewer myelinating cells. Similarly, P0-P1 Boc mutant mouse pups had a deficit of cells expressing the OPC markers Olig2 and PDGFRa in the dorsal forebrain (Zakaria et al 2019). Thus, progenitor populations in different regions of the developing nervous system may have a common requirement for Boc function in formation of OPCs from neural progenitors.…”

Astrocytes and Microglia as Major Players of Myelin Production in Normal and Pathological Conditions

“…This activation implicates changes in morphology and transcriptional profiles of the cells. The failure of microglia to convert from a ''resting state'' with a branched-like morphology to an ''activated state'' with an amoeboid-like morphology was namely observed upon knocking down either the β-galactoside-binding lectin Galectin-3 (Reichert and Rotshenker, 2019) or one of the receptors of the secreted proteins Sonic hedgehog, the protein Boc (Zakaria et al, 2019).…”

X chromosome-dependent disruption of placental regulatory networks in hybrid dwarf hamsters

“…Similarly, the Plexin domain containing 2 gene (Plxdc2) encodes an endothelial cell-surface transmembrane receptor (Cheng et al 2014) that is often co-expressed with Wnt signaling genes (Miller et al 2007). Other candidate hub genes play roles in cell-cell adhesion and differentiation (Wilson et al 2007;Jang et al 2016;Zakaria et al 2019), immune function (Astarita et al 2012;Li et al 2013;Wang et al 2013;Chistiakov et al 2017), nutrient metabolism and delivery (Schmidt et al 1992;Malabanan and Blind 2016), and transcriptional regulation (Ferreira et al 2019).…”