QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 25, 2008, 28(26):6703-6713; doi:10.1523/JNEUROSCI.0215-08.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Cebolla, B. Articles by Vallejo, M. PubMed PubMed Citation Articles by Cebolla, B. Articles by Vallejo, M.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
DREAM Mediates cAMP-Dependent, Ca²⁺-Induced Stimulation of GFAP Gene Expression and Regulates Cortical Astrogliogenesis

Beatriz Cebolla,^1 * Antonio Fernández-Pérez,^1 * Gertrudis Perea,² Alfonso Araque,² and Mario Vallejo¹

¹Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas/Universidad Autónoma de Madrid, 28029 Madrid, Spain, and ²Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain

Correspondence should be addressed to Dr. Mario Vallejo, Instituto de Investigaciones Biomédicas Alberto Sols, Calle Arturo Duperier 4, 28029 Madrid, Spain. Email: mvallejo{at}iib.uam.es

In the developing mouse brain, once the generation of neurons is mostly completed during the prenatal period, precisely coordinated signals act on competent neural precursors to direct their differentiation into astrocytes, which occurs mostly after birth. Among these signals, those provided by neurotrophic cytokines and bone morphogenetic proteins appear to have a key role in triggering the neurogenic to gliogenic switch and in regulating astrocyte numbers. In addition, we have reported previously that the neurotrophic peptide pituitary adenylate cyclase-activating polypeptide (PACAP) is able to promote astrocyte differentiation of cortical precursors via activation of a cAMP-dependent pathway. Signals acting on progenitor cells of the developing cortex to generate astrocytes activate glial fibrillary acidic protein (GFAP) gene expression, but the transcriptional mechanisms that regulate this activation are unclear. Here, we identify the previously known transcriptional repressor downstream regulatory element antagonist modulator (DREAM) as an activator of GFAP gene expression. We found that DREAM occupies specific sites on the GFAP promoter before and after differentiation is initiated by exposure of cortical progenitor cells to PACAP. PACAP raises intracellular calcium concentration via a mechanism that requires cAMP, and DREAM-mediated transactivation of the GFAP gene requires the integrity of calcium-binding domains. Cortical progenitor cells from dream^–/– mice fail to express GFAP in response to PACAP. Moreover, the neonatal cortex of dream^–/– mice exhibits a reduced number of astrocytes and increased number of neurons. These results identify the PACAP-cAMP-Ca²⁺-DREAM cascade as a new pathway to activate GFAP gene expression during astrocyte differentiation.

Key words: glial fibrillary acidic protein; DREAM; gliogenesis; cAMP; calcium; transcription

---

Received Jan. 17, 2008; revised May 12, 2008; accepted May 20, 2008.

Correspondence should be addressed to Dr. Mario Vallejo, Instituto de Investigaciones Biomédicas Alberto Sols, Calle Arturo Duperier 4, 28029 Madrid, Spain. Email: mvallejo{at}iib.uam.es

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help