Evidence That DDR1 Promotes Oligodendrocyte Differentiation during Development and Myelin Repair after Injury

Abstract

Oligodendrocytes generate myelin sheaths vital for the formation, health, and function of the central nervous system. Mounting evidence suggests that receptor tyrosine kinases (RTKs) are crucial for oligodendrocyte differentiation and myelination in the CNS. It was recently reported that discoidin domain receptor 1 (Ddr1), a collagen-activated RTK, is expressed in oligodendrocyte lineage. However, its specific expression stage and functional role in oligodendrocyte development in the CNS remain to be determined. In this study, we report that Ddr1 is selectively upregulated in newly differentiated oligodendrocytes in the early postnatal CNS and regulates oligodendrocyte differentiation and myelination. Ddr1 knock-out mice of both sexes displayed compromised axonal myelination and apparent motor dysfunction. Ddr1 deficiency alerted the ERK pathway, but not the AKT pathway in the CNS. In addition, Ddr1 function is important for myelin repair after lysolecithin-induced demyelination. Taken together, the current study described, for the first time, the role of Ddr1 in myelin development and repair in the CNS, providing a novel molecule target for the treatment of demyelinating diseases.

Conditional Deletion of Foxg1 Delayed Myelination during Early Postnatal Brain Development

“…Signal detection was performed using the NBT/BCIP substrate. The plasmid used to synthesize the probes of mouse Mbp, Plp1, and Pdgfrα in this study was generously provided by Dr. Mengsheng Qiu from Hangzhou Normal University [ 55 ]. Images were acquired using a bright field microscope (Olympus BX53, Japan) and a digital slide scanner (Olympus VS200, Japan).…”

“…After hybridization, the sections were washed three times in 2× SSC at 65 • C for 30 min each, followed by blocking with 5% sheep serum and incubation with anti-digoxigenin-AP antibody (Roche, 1:5000, 11333089001) overnight at 4 • C. Signal detection was performed using the NBT/BCIP substrate. The plasmid used to synthesize the probes of mouse Mbp, Plp1, and Pdgfrα in this study was generously provided by Dr. Mengsheng Qiu from Hangzhou Normal University [55]. Images were acquired using a bright field microscope (Olympus BX53, Japan) and a digital slide scanner (Olympus VS200, Japan).…”

β-Catenin and SOX2 Interaction Regulate Visual Experience-Dependent Cell Homeostasis in the Developing Xenopus Thalamus

“…C57BL/6 laboratory mice were kept in a controlled environment with a regulated temperature of 22 ± 1 • C and a 12 h light/dark cycle. The mice's overall health was monitored daily throughout the study [90]. For the experiments, the mice were humanely euthanized using Avertin-induced deep anesthesia.…”