engleski

JAK-1/Smad signaling dependent genes expression associated with neurogenic to astrogliogenic transition point of brain development

To address the question on the role of a Jak-1 molecule in the TGF-beta controlled sequential process of brain development, we have used cell lines either deficient or enriched in Jak-1. Upon their transfection with TGF-beta receptor associated molecules - Flagged Smad-3, -2 or -1, the expression pattern of Neurogenin 1 and Glial Fibrillary Acidic Protein (GFAP) related to NF-kB activation has been followed. We found that no expression of Neurogenin 1 or GFAP can be induced in mutant cells following single transfection. However, based on the p65 nuclear translocation, we have found that NF-kB transcription factor becomes activated following transfection with the plasmid encoding Smad1 which plays a central role in the alternative TGF-beta signaling triggered via ALK-1 receptor. Decreased Smad-1 mRNA expression in the same cells upon transfection with plasmid encoding Smad-2, indicates the Jak-1/Smad2 dependent signaling likely interfere with ALK-1 mediated pathway to which a neuroprotective role has been assigned.

cytokine signaling; brain development; gliosis; brain injuries

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