Evolution of the Nervous System Extrapolated from Ctenophore and the Resurrection of Golgi’s Reticular Theory?

For over a century,the structure and evolution of the nervous system have been at the center of debate among biologists.In the 19th century,Camillo Golgi first proposed that the nervous system is a syncytial continuum,with neurons being directly connected with shared cell membranes and cytoplasm[1].This concept is known as the reticular theory(also referred to as the syncytial theory).However,this view was later challenged by Santiago Ramon y Cajal,who put forward the neuronal doctrine[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.

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.

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.

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.

Aberrant nuclear lamina contributes to the malignancy of human gliomas

Glioma is the most common type of tumor in the central nervous system, accounting for around 80% of all malignant brain tumors. Previous studies showed a significant association between nuclear morphology and the malignant progress of gliomas. By virtue of integrated proteomics and genomics analyses as well as experimental validations, we identify three nuclear lamin genes(LMNA, LMNB1, and LMNB2) that are significantly upregulated in glioma tissues compared with normal brain tissues. We show that elevated expressions of LMNB1, LMNB2, and LMNA in glioma cells are highly associated with the rapid progression of the disease and the knockdown of LMNB1, LMNB2, and LMNA dramatically suppresses glioma progression in both in vitro and in vivo mouse models. Moreover, the repression of glioma cell growth by lamin knockdown is mediated by the p Rb-mediated G1-S inhibition. On the contrary, overexpression of lamins in normal human astrocytes dramatically induced nuclear morphological aberrations and accelerated cell growth. Together, our multi-omics-based analysis has revealed a previously unrecognized role of lamin genes in gliomagenesis, providing a strong support for the key link between aberrant tumor nuclear shape and the survival of glioma patients. Based on these findings, lamins are proposed to be potential oncogene targets for therapeutic treatments of brain tumors.