Sp4-dependent repression of neurotrophin-3 limits dendritic branching
Por:
Ramos B, Valin, Alvaro, Sun, Xinxin and Gill, Grace
Publicada:
1 sep 2009
Resumen:
Regulation of neuronal gene expression is critical to establish
functional connections in the mammalian nervous system. The
transcription factor Sp4 regulates dendritic patterning during
cerebellar granule neuron development by limiting branching and
promoting activity-dependent pruning. Here, we investigate
neurotrophin-3 (NT3) as a target gene important for Sp4-dependent
dendritic morphogenesis. We found that Sp4 overexpression reduced NT3
promoter activity whereas knockdown of Sp4 increased NT3 promoter
activity and mRNA. Moreover, Sp4 bound to the NT3 promoter in vivo,
supporting a direct role for Sp4 as a repressor of NT3 expression.
Addition of exogenous NT3 promoted dendritic branching in cerebellar
granule neurons. Furthermore, sequestering NT3 blocked the continued
addition of dendritic branches observed upon Sp4 knockdown, but had no
effect on dendrite pruning. These findings demonstrate that, during
cerebellar granule neuron development, Sp4-dependent repression of
neurotrophin-3 is required to limit dendritic branching and thereby
promote acquisition of the mature dendritic pattern. (C) 2009 Elsevier
Inc. All rights reserved.
Filiaciones:
Ramos B:
Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA
Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
Fundacio St Joan Dieu, Ctr Invest Red Salud Mental CIBERSAM, St Joan Deu SSM, Barcelona 08950, Spain
Valin, Alvaro:
Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA
Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
Sun, Xinxin:
Tufts Univ, Sch Med, Sackler Sch Biomed Sci, Genet Program, Boston, MA 02111 USA
Gill, Grace:
Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA
Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
Tufts Univ, Sch Med, Sackler Sch Biomed Sci, Genet Program, Boston, MA 02111 USA
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