title: ATF3 is a novel nuclear marker for migrating ependymal stem cells in the rat spinal cord.
abstract: The present study identified ATF3 as a novel dynamic marker for ependymal stem/progenitor cells (nestin, vimentin and SOX2 positive) around the central canal of the neonatal or adult rat spinal cord. While quiescent ependymal cells showed cytoplasmic ATF3 expression, during 6-24h in vitro these cells mobilized and acquired intense nuclear ATF3 staining. Their migratory pattern followed a centrifugal pathway toward the dorsal and ventral funiculi, reminiscent of the rostral migratory stream of the brain subventricular stem cells. Thus, the chain cell formation was, by analogy, termed funicular migratory stream (FMS). The FMS process preceded the strong proliferation of ependymal cells occurring only after 24h in vitro. Pharmacological inhibition of MAPK-p38 and JNK/c-Jun (upstream effectors of ATF3 activation) prevented the FMS mobilization of ATF3 nuclear-positive cells. Excitotoxicity or ischemia-like conditions, reported to evoke neuronal and glial injury, did not further enhance migration of ependymal cells at 24h, suggesting that, at this early stage of damage, the FMS phenomenon had peaked and that more extensive repair processes are delayed beyond this time point. ATF3 is, therefore, useful to identify activation and migration of endogenous stem cells of the rat spinal cord in vitro.
authors.affiliation: Neuroscience Dept., International School for Advanced Studies (SISSA), Trieste, Italy; SPINAL (Spinal Person Injury Neurorehabilitation Applied Laboratory), Istituto di Medicina Fisica e Riabilitazione, Udine, Italy; Department of Biotechnology, University of Rijeka, Rijeka, Croatia. Electronic address: mirandamp@uniri.hr.
authors.forename: Miranda
authors.initials: M
authors.lastname: Mladinic
authors.affiliation: Neuroscience Dept., International School for Advanced Studies (SISSA), Trieste, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bianchetti
authors.affiliation: Neuroscience Dept., International School for Advanced Studies (SISSA), Trieste, Italy; Department of Biotechnology, University of Rijeka, Rijeka, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Dekanic
authors.affiliation: Neuroscience Dept., International School for Advanced Studies (SISSA), Trieste, Italy.
authors.forename: Graciela L
authors.initials: GL
authors.lastname: Mazzone
authors.affiliation: Neuroscience Dept., International School for Advanced Studies (SISSA), Trieste, Italy; SPINAL (Spinal Person Injury Neurorehabilitation Applied Laboratory), Istituto di Medicina Fisica e Riabilitazione, Udine, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Nistri
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D004805:Ependyma / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat