A molecular pathway involved in the generation of microtubule-associated protein 2-positive cells from microglia.
We have recently demonstrated that microglia as multipotential stem cells give rise to microtubule-associated protein 2 (MAP2)-positive and glial fibrillary acidic protein (GFAP)-positive cells and that microglia-derived MAP2-positive cells possess properties of functional neurons. In this study, we investigated the molecular pathways involved in the generation of microglia-derived MAP2-positive and GFAP-positive cells. Western blot analyses demonstrated that expression levels of Id2 protein, an inhibitory basic helix-loop-helix transcription factor of the inhibitor of differentiation and DNA binding family, and Smad proteins were upregulated under differentiation conditions. Immunocytochemical analyses demonstrated that the generation of MAP2-positive and GFAP-positive cells from microglia was promoted by bone morphogenetic proteins (BMPs) and was inhibited by noggin which is a BMP antagonist, Smad4 siRNA and Id2 siRNA. These results indicate that activation of BMP signaling through Smad and Id2 proteins is one of the molecular pathways involved in the generation of microglia-derived MAP2-positive and GFAP-positive cells.
Niidome
Tetsuhiro
T
Department of Neuroscience for Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida-Shimoadachi-Cho, Sakyo-Ku, Kyoto 606-8501, Japan. tniidome@pharm.kyoto-u.ac.jp
Matsuda
Satoru
S
Nonaka
Hideki
H
Akaike
Akinori
A
Kihara
Takeshi
T
Sugimoto
Hachiro
H
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044967:Serum; D051901:Smad4 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D019485:Bone Morphogenetic Proteins; D005904:Glial Fibrillary Acidic Protein; C497451:Id2 protein, rat; D051797:Inhibitor of Differentiation Protein 2; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D051901:Smad4 Protein; C490811:Smad4 protein, rat