TAPP1 Represses the Differentiation of Oligodendrocyte and its Deficiency Accelerates Myelin Regeneration after Demyelinating Injuries

Dear Editor,Myelin,the lipid-rich insulation that supports the integrity of axons,enables rapid conduction of nerve impulses and information flow to distant brain areas[1].Oligodendrocytes(OLs)are glial cells that myelinate axons with specialized lipid membrane extensions[2].OL progenitor cells(OPCs)arise from neural stem cells[3],and undergo proliferation before terminal differentiation and eventual myelination.Impairment at any stage of OL development can affect myelin formation.

AATYK is a Novel Regulator of Oligodendrocyte Differentiation and Myelination

Oligodendrocytes(OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK(apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYKdeficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.

MYRF:A Mysterious Membrane-bound Transcription Factor Involved in Myelin Development and Human Diseases

The myelin regulatory factor gene(MYRF)encodes a protein evolutionarily conserved from invertebrates to vertebrates,representing a novel type of membrane-bound transcriptional factor(MBTF).In vertebrates,MYRF protein is required for myelin development and maintenance[1,2].

Genetic Evidence that Dorsal Spinal Oligodendrocyte Progenitor Cells are Capable of Myelinating Ventral Axons Effectively in Mice

In the developing spinal cord,the majority of oligodendrocyte progenitor cells(OPCs)are induced in the ventral neuroepithelium under the control of the Sonic Hedgehog(Shh)signaling pathway,whereas a small subset of OPCs are generated from the dorsal neuroepithelial cells independent of the Shh pathway.Although dors allyderived OPCs(dOPCs)have been shown to participate in local axonal myelination in the dorsolateral regions during development,it is not known whether they are capable of migrating into the ventral region and myelinating ventral axons.In this study,we confirmed and extended the previous study on the developmental potential of dOPCs in the absence of ventrally-derived OPCs(vOPCs).In NestinSmo conditional knockout(cKO)mice,when ventral oligodendrogenesis was blocked,dOPCs were found to undergo rapid amplification,spread to ventral spinal tissue,and eventually differentiated into myelinating OLs in the ventral white matter with a temporal delay,providing genetic evidence that dOPCs are capable of myelinating ventral axons in the mouse spinal cord.

TAPP1 inhibits the differentiation of oligodendrocyte precursor cells via suppressing the Mek/Erk pathway

Oligodendrocytes(OLs) are glial cells that form myelin sheaths around axons in the central nervous system(CNS).Loss of the myelin sheath in demyelinating and neurodegenerative diseases can lead to severe impairment of movement.Understanding the extracellular signals and intracellular factors that regulate OL differentiation and myelination during development can help to develop novel strategies for enhancing myelin repair in neurological disorders.Here,we report that TAPP1 was selectively expressed in differentiating OL precursor cells(OPCs).TAPP1 knockdown promoted OL differentiation and myelin gene expression in culture.Conversely,over-expression of TAPP1 in immature OPCs suppressed their differentiation.Moreover,TAPP1 inhibition in OPCs altered the expression of Erk1/2 but not AKT.Taken together,our results identify TAPP1 as an important negative regulator of OPC differentiation through the Mek/Erk signaling pathway.

Nuclear Factor I/A Controls A-fiber Nociceptor Development

Noxious mechanical information is transmitted through molecularly distinct nociceptors,with pinprickevoked sharp sensitivity via A-fiber nociceptors marked by developmental expression of the neuropeptide Y receptor 2(Npy2 r)and von Frey filament-evoked punctate pressure information via unmyelinated C fiber nociceptors marked by MrgprD.However,the molecular programs controlling their development are only beginning to be understood.Here we demonstrate that Npy2 r-expressing sensory neurons are in fact divided into two groups,based on transient or persistent Npy2 r expression.Npy2 r-transient neurons are myelinated,likely including A-fiber nociceptors,whereas Npy2 r-persistent ones belong to unmyelinated pruriceptors that co-express Nppb.We then showed that the transcription factors NFIA and Runx1 are necessary for the development of Npy2 r-transient A-fiber nociceptors and MrgprD^+C-fiber nociceptors,respectively.Behaviorally,mice with conditional knockout of Nfia,but not Runx1 showed a marked attenuation of pinprick-evoked nocifensive responses.Our studies therefore identify a transcription factor controlling the development of myelinated nociceptors.

Immunological Markers for Central Nervous System Glia

Glial cells in the central nervous system(CNS)are composed of oligodendrocytes,astrocytes and microglia.They contribute more than half of the total cells of the CNS,and are essential for neural development and functioning.Studies on the fate specification,differentiation,and functional diversification of glial cells mainly rely on the proper use of cell-or stage-specific molecular markers.However,as cellular markers often exhibit different specificity and sensitivity,careful consideration must be given prior to their application to avoid possible confusion.Here,we provide an updated overview of a list of well-established immunological markers for the labeling of central glia,and discuss the cell-type specificity and stage dependency of their expression.