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TGF‐β1/SMAD signaling induces astrocyte fate commitment in vitro : Implications for radial glia development
Author(s) -
Stipursky Joice,
Gomes Flávia Carvalho Alcantara
Publication year - 2007
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20522
Subject(s) - astrocyte , nestin , biology , microbiology and biotechnology , progenitor cell , neurogenesis , transforming growth factor , glial fibrillary acidic protein , cellular differentiation , smad , stem cell , neural stem cell , neuroscience , immunology , central nervous system , immunohistochemistry , biochemistry , gene
Radial glial (RG) cells are specialized type of cell, which functions as neuronal precursors and scaffolding guides to migrating neurons during cerebral cortex development. After neurogenesis and migration are completed, most of RG cells transform into astrocytes. Mechanism and molecules involved in this process are not completely elucidated. We previously demonstrated that neurons activate the promoter of the astrocyte maturation marker GFAP in astrocytes by secretion of transforming growth factor beta 1 (TGF‐β1) in vitro . Here, we studied the role of neurons and TGF‐β1 pathway in RG differentiation. To address this question, we employed cortical progenitor cultures enriched in GLAST/nestin double‐labeled cells, markers of RG cells. TGF‐β1 and conditioned medium derived from neuron‐astrocyte cocultures (CM) decreased the number of cells expressing the precursor marker nestin and increased that expressing GFAP in cortical progenitor cultures. These events were impaired by addition of neutralizing antibodies against TGF‐β1. Increase in the number of GFAP positive cells was associated with Smads 2/3 nuclear translocation, a hallmark of TGF‐β1 pathway activation. PCR‐assays revealed a decrease in the levels of mRNA for the RG marker, BLBP (brain lipid binding protein), due to TGF‐β1 and CM treatment. We further identified TGF‐β1 receptor in cortical progenitor cultures suggesting that these cells might be target for TGF‐β1 during development. Our work provides strong evidence that TGF‐β1 might be a novel factor involved in RG‐astrocyte transformation and highlights the role of neuron‐glia interaction in this process. © 2007 Wiley‐Liss, Inc.