Epidermal growth factor promotes oligodendrocyte process formation and regrowth after injury.
Oligodendrocytes (OLs) form myelin within the central nervous system and are targets in numerous demyelinating diseases and injuries. OLs grown in culture maintain the developmental timetable which occurs in vivo and mature into cells with a relatively normal phenotype. In this study, cultured cells are used to test whether EGF can modulate process formation in OLs both before and after transection injury. EGF had no effect on the formation of new processes by OLs at any stage of development. To test the effect of EGF on process outgrowth after injury, mature OLs were selected and injured by laser transection of a single process, then imaged at 24-h intervals for 120 h. EGF promoted the recovery and regrowth of injured processes and also significantly increased outgrowth in uninjured processes. As well, it increased the number of new sprouts formed by OLs after injury. Results suggest that the effects of EGF on process outgrowth are a consequence of EGF interaction with a signaling pathway that is specifically activated within injured OLs. The potent effect of EGF on OL process formation after an injury suggests that modulation of the signaling pathways involved might provide a mechanism to promote remyelination.
Knapp
Pamela E
PE
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA. peknapp@uky.edu
Adams
Mary H
MH
D000818:Animals; D001369:Axons; D002454:Cell Differentiation; D048429:Cell Size; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D051379:Mice; D008858:Microscopy, Phase-Contrast; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051076:Proto-Oncogene Proteins c-fyn; D012038:Regeneration / Q000187:drug effects*; D015398:Signal Transduction; D013997:Time Factors; D014947:Wounds and Injuries
D011518:Proto-Oncogene Proteins; D004815:Epidermal Growth Factor; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn