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Astroglia genesis in vitro: distinct effects of retinoic acid in different phases of neural stem cell differentiaion
Authors:Nóra Hádinger  Balázs V Varga  Sára Berzsenyi  Zsuzsanna KörnyeiEmília Madarász  Balázs Herberth
Institution:Institute of Experimental Medicine of Hungarian Academy of Sciences, Budapest, Hungary
Abstract:In the developing CNS, the manifestation of the macroglial phenotypes is delayed behind the formation of neurons. The “neurons first – glia second” principle seems to be valid for neural tissue differentiation throughout the neuraxis, but the reasons behind are far from clear. In the presented study, the mechanisms of this timing were investigated in vitro, in the course of the neural differentiation of one cell derived NE-4C neuroectodermal stem and P19 embryonic carcinoma cells. The data demonstrated that astrocyte formation coincided in time with the maturation of postmitotic neurons, but the close vicinity of neurons did not initate astrocyte formation before schedule. All-trans retinoic acid, a well-known inducer of neuronal differentiation, on the other hand, blocked effectively the astroglia production if present in defined stages of the in vitro neuroectodermal cell differentiation. According to the data, retinoic acid plays at least a dual role in astrogliogenesis: while it is needed for committing neural progenitors for a future production of astrocytes, it prevents premature astrogliogenesis by inhibiting the differentiation of primed glial progenitors.
Keywords:blbp  brain lipid-binding protein  BMP  bone morphogenetic protein  BrdU  -brome-2&prime" target="_blank">5-brome-2&prime  -deoxyuridine" target="_blank">-deoxyuridine  CM  conditioned media  CNS  central nervous system  CNTF  ciliary neurotrophic factor  EC  embryonal carcinoma  GFAP  glial fibrillary acidic protein  GFP  green fluorescent protein  glast  glutamate-aspartate transporter  LIF  leukemia inhibitory factor  math2  mammalian atonal homologue 2  Ngn2  neurogenin 2  RA  all-trans retinoic acid  RAR  retinoic acid receptor  RARE  retinoic acid responsive element  SSEA  stage specific embryonic antigen 1
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