Prolactin (PRL), an anterior pituitary hormone with neurogenic properties associated with pregnancy, has been implicated in oligodendrocyte proliferation during gestation, contributing to increased myelination in the maternal brain. However, PRL is elevated during lactation as well, suggesting that the postpartum (PP) period may contribute to additional gliogenesis in lactating females. In the ...

Here, we present mechanisms for the inhibition of oligodendendrocyte precursor cell (OPC) differentiation, a biological function of neural extracellular matrix (ECM). The differentiation of oligodendrocytes is orchestrated by a complex set of stimuli. In the present study, we investigated the signaling pathway elicited by the ECM glycoprotein tenascin C (Tnc). Tnc substrates inhibit myelin basi...

In order to determine the signals that initiate axon myelination in the CNS, we have chronicled the differentiation of oligodendrocytes in the rat optic nerve and related this to the time course and spatial gradient seen for optic axon myelination. By using markers specific to the varying stages of oligodendrocyte differentiation we found that oligodendrocyte progenitor cells, present throughou...

Oligodendrocyte development is tightly controlled by a variety of extracellular growth and differentiation factors. The mitogen-activated protein kinases (MAPKs), ERK1 and ERK2, are critical intracellular signaling molecules important for transducing these extracellular signals. The extracellular signal-regulated kinases (ERKs) are ubiquitously expressed, coordinately regulated, and highly simi...

Oligodendrocytes form myelin around axons of the central nervous system, enabling saltatory conduction. Recent work has established that axons can regulate certain aspects of oligodendrocyte development and myelination, yet remarkably oligodendrocytes in culture retain the ability to differentiate in the absence of axons and elaborate myelin sheaths around synthetic axon-like substrates. It rem...

Barnett and Prineas recently reported new morphological findings in the brain of a 14-year-old patient with relapsing-remitting multiple sclerosis (MS) who died within 24 hours of the onset of a new symptomatic and fatal brainstem lesion. Within this early lesion, they observed extensive oligodendrocyte cell death which they attributed to apoptosis. Strikingly, no T lymphocytes were detected in...

This study addresses the role of Sonic hedgehog (Shh) in promoting the generation of oligodendrocytes in the mouse telencephalon. We show that in the forebrain, expression of the early oligodendrocyte markers Olig2, plp/dm20 and PDGFR(alpha) corresponds to regions of Shh expression. To directly test if Shh can induce the development of oligodendrocytes within the telencephalon, we use retrovira...

Leukemia/lymphoma-related factor (LRF), a zinc-finger transcription factor encoded by Zbtb7a, is a protooncogene that regulates differentiation in diverse cell lineages, and in the CNS, its function is relatively unexplored. This study is the first to examine the role of LRF in CNS pathology. We first examined LRF expression in a murine viral model of spinal cord demyelination with clinically r...

Current approaches to derive oligodendrocytes from human pluripotent stem cells (hPSCs) need extended exposure of hPSCs to growth factors and small molecules, which limits their clinical application because of the lengthy culture time required and low generation efficiency of myelinating oligodendrocytes. Compared to extrinsic growth factors and molecules, oligodendrocyte differentiation and ma...