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A New Axonal Splice Variant of HDGF-related protein 3 Increases Mature Oligodendrocyte Numbers


In the central nervous system, axons are myelinated by oligodendrocytes (OLs). However, though our understanding of OL biology is increasing, the signals that emanate from the axons and modulate myelination are still poorly understood. Previous studies have found that HRP3-II, a newly identified isoform of the hepatoma-derived growth factor (HDGF) family, shows peak expression in the axons of spinal motor neurons before and during the myelination period. Furthermore, overexpression of HRP3-II increased Schwann cell proliferation and myelination, suggesting its importance for regulating the local pool of Schwann cells. Therefore, our goal is to determine whether HRP3-II also plays a critical role in regulating OLs in the central nervous system (CNS) using a recently developed CNS myelination model. The model is based on co-culturing mouse embryonic stem cell derived cortical neurons and OLs in microfluidic devices. We overexpressed HRP3-II in the neurons using a viral construct in the co-cultures. The average number of Myelin Basic Protein-positive OLs was significantly larger in the HRP3-II overexpressing co- cultures compared to controls; however, a similar increase was not seen on myelination in the HRP3-II overexpressing co-cultures, suggesting its role in the proliferation and/ or maturation of OLs

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