Neuro-glia interaction effects on GFAP gene: a novel role for transforming growth factor-beta1.
Central nervous system (CNS) development is highly guided by microenvironment cues specially provided by neuron-glia interactions. By using a transgenic mouse bearing part of the gene promoter of the astrocytic maturation marker GFAP (glial fibrillary acidic protein) linked to the beta-galactosidase (beta-Gal) reporter gene, we previously demonstrated that cerebral cortical neurons increase transgenic beta-Gal astrocyte number and activate GFAP gene promoter by secretion of soluble factors in vitro. Here, we identified TGF-beta1 as the major mediator of this event. Identification of TGF-beta1 in neuronal and astrocyte extracts revealed that both cell types might synthesize this factor, however, addition of neurons to astrocyte monolayers greatly increased TGF-beta1 synthesis and secretion by astrocytes. Further, by exploiting the advantages of cell culture system we investigated the influence of neuron and astrocyte developmental stage on such interaction. We demonstrated that younger neurons derived from 14 embryonic days wild-type mice were more efficient in promoting astrocyte differentiation than those derived from 18 embryonic days mice. Similarly, astrocytes also exhibited timed-schedule developed responsiveness to neuronal influence with embryonic astrocytes being more responsive to neurons than newborn and late postnatal astrocytes. RT-PCR assays identified TGF-beta1 transcripts in young but not in old neurons, suggesting that inability to induce astrocyte differentiation is related to TGF-beta1 synthesis and secretion. Our work reveals an important role for neuron-glia interactions in astrocyte development and strongly implicates the involvement of TGF-beta1 in this event.
de Sampaio e Spohr
Tânia Cristina Leite
TC
Instituto de Ciências Biomédicas, Departamento de Anatomia, Universidade Federal do Rio de Janeiro, 21941-590, Rio de Janeiro, Brazil.
Martinez
Rodrigo
R
da Silva
Elen Federowicz
EF
Neto
Vivaldo Moura
VM
Gomes
Flávia Carvalho Alcantara
FC
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D005904:Glial Fibrillary Acidic Protein; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor