Project description:Disorders that disrupt myelin during development or in adulthood, such as multiple sclerosis and peripheral neuropathies, lead to severe pathologies, illustrating myelin’s crucial role in normal neural functioning. However, although our understanding of Schwann cell and oligodendrocyte biology is increasing, the signals that emanate from axons and regulate myelination remain largely unknown. To identify the core components of the myelination process, we adopted a microarray analysis approach combined with laser capture microdissection of spinal motoneurons (MNs) during the myelinogenic phase of development.
Project description:miRNAs are critical for myelination in the peripheral nervous system. We report the differential expression of miRNAs during myelination in sciatic nerves of wild-type mice. This data serves as a starting point to identify physiologically relevant regulatory miRNAs in the peripheral nervous system.
Project description:Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)—a transcription factor known to regulate expression of actin and actin regulators in other cell types—as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the fundamental role of SRF in oligodendrocyte lineage cells. Here we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in OPCs and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies a novel pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.
Project description:Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)—a transcription factor known to regulate expression of actin and actin regulators in other cell types—as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the fundamental role of SRF in oligodendrocyte lineage cells. Here we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in OPCs and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies a novel pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.
Project description:Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)—a transcription factor known to regulate expression of actin and actin regulators in other cell types—as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the fundamental role of SRF in oligodendrocyte lineage cells. Here we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in OPCs and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies a novel pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.
Project description:We performed genome-wide profiling of Tcf7l2 occupancy during oligodendrocyte differentiation and identified the key enzymes involved in cholesterol metabolism and essential for CNS myelination. Examination of Tcf7l2 chIP-seq in oligodendrocyte progenitor cell and 2 differentiation oligodendrocytes.
Project description:To obtain the dynamic gene expression of myelinating Schwann cells, we have employed gene expression profiling microarray as a discovery platform to analyze the gene expression of Schwann cells in different stages of myelination in an DRG neuron and SC co-culture myelinating model. Rat Schwann cells and dorsal root ganglion (DRG) neurons were cocultured and induced myelination in DMEM medium containing 15% FBS, 50 ng/ml NGF and 50 μg/ml L-ascorbic acid for 21d. During the co-cultivation, myelinating SCs at different stages dissected by Laser microdissection (LMD) in myelination model (i.e. co-culture 1d, 3d, 7d, 14d, 21d), the Schwann cells without co-culture as control samples (i.e. co-culture 0d). The results from Euclidean distance matrix, principal component analysis, and hierarchical clustering indicated that 2 nodal transitions in temporal gene expressions could segregate 3 distinct transcriptional phases within the period of DRG/SC co-culture 21 days. The 3 phases were designated as “premyelination”, “myelination”, and “mature phase”, respectively, by referring to morphological observation of post co-culture changes and gene ontology (GO) analysis.
Project description:We performed genome-wide profiling of Tcf7l2 occupancy during oligodendrocyte differentiation and identified the key enzymes involved in cholesterol metabolism and essential for CNS myelination.