Hedgehog: A Key Signaling in the Development of the Oligodendrocyte Lineage

Abstract

The Hedgehog morphogen aroused an enormous interest since it was characterized as an essential signal for ventral patterning of the spinal cord two decades ago. The pathway is notably implicated in the initial appearance of the progenitors of oligodendrocytes (OPCs), the glial cells of the central nervous system which after maturation are responsible for axon myelination. In accordance with the requirement for Hedgehog signaling in ventral patterning, the earliest identifiable cells in the oligodendrocyte lineage are derived from the ventral ventricular zone of the developing spinal cord and brain. Here, we present the current knowledge about the involvement of Hedgehog signaling in the strict spatial and temporal regulation which characterizes the initiation and progression of the oligodendrocyte lineage. We notably describe the ability of the Hedgehog signaling to tightly orchestrate the appearance of specific combinations of genes in concert with other pathways. We document the molecular mechanisms controlling Hedgehog temporal activity during OPC specification. The contribution of the pathway to aspects of OPC development different from their specification is also highlighted especially in the optic nerve. Finally, we report the data demonstrating that Hedgehog signaling-dependency is not a universal situation for oligodendrocyte generation as evidenced in the dorsal spinal cord in contrast to the dorsal forebrain.

Stage‐specific regulation of oligodendrocyte development by Hedgehog signaling in the spinal cord

“…Noticeably, it was shown that Olig1 cre induced tdTomato fluorescence in other cell types, including motor neurons (MNs) (Figure a,b). Hh signaling has been demonstrated to play pivotal roles in the control of MN‐OPC fate switch (Traiffort et al, ), prompting us to speculate that the neonatal death of Olig1‐SmoM2 might be related to defective MN development. To evaluate the MN development in Olig1‐SmoM2 embryos, we examined the expression of MN‐specific markers, Islet1 and choline acetyltransferase (ChAT).…”

Oligodendrocytes in intracerebral hemorrhage

“…Biochemically, oligodendrocyte‐lineage cells express a variety of molecular markers at distinct differentiation stages. Upon lineage specification, Olig1/2, Sox10 (SRY‐Box transcription factor 10), and Nkx2.2 are substantially upregulated and persist throughout the life of oligodendrocyte‐lineage cells . Thus, these molecules are used as markers for oligodendrocyte‐lineage cells.…”

“…Thus, these molecules are used as markers for oligodendrocyte‐lineage cells. Classical OPC markers include NG2 (neuron‐glial antigen 2), PDGFRα, and Id2/4 . It should be noted that these markers are not OPC‐specific.…”

“…Upon lineage specification, Olig1/2, Sox10 (SRY-Box transcription factor 10), and Nkx2.2 are substantially upregulated and persist throughout the life of oligodendrocyte-lineage cells. 7,13,[31][32][33][34][35][36][37][38][39] Thus, these molecules are used as markers for oligodendrocyte-lineage cells. Classical OPC markers include NG2 (neuron-glial antigen 2), PDGFRα, and Id2/4.…”

“…Classical OPC markers include NG2 (neuron-glial antigen 2), PDGFRα, and Id2/4. 34,[40][41][42][43][44][45] It should be noted that these markers are not OPC-specific. For example, NG2 is also expressed in mural cells and PDGFRα is also found in fibroblasts.…”