title: Satb1 ablation alters temporal expression of immediate early genes and reduces dendritic spine density during postnatal brain development.
abstract: Complex behaviors, such as learning and memory, are associated with rapid changes in gene expression of neurons and subsequent formation of new synaptic connections. However, how external signals are processed to drive specific changes in gene expression is largely unknown. We found that the genome organizer protein Satb1 is highly expressed in mature neurons, primarily in the cerebral cortex, dentate hilus, and amygdala. In Satb1-null mice, cortical layer morphology was normal. However, in postnatal Satb1-null cortical pyramidal neurons, we found a substantial decrease in the density of dendritic spines, which play critical roles in synaptic transmission and plasticity. Further, we found that in the cerebral cortex, Satb1 binds to genomic loci of multiple immediate early genes (IEGs) (Fos, Fosb, Egr1, Egr2, Arc, and Bdnf) and other key neuronal genes, many of which have been implicated in synaptic plasticity. Loss of Satb1 resulted in greatly alters timing and expression levels of these IEGs during early postnatal cerebral cortical development and also upon stimulation in cortical organotypic cultures. These data indicate that Satb1 is required for proper temporal dynamics of IEG expression. Based on these findings, we propose that Satb1 plays a critical role in cortical neurons to facilitate neuronal plasticity.
authors: Lawrence Berkeley National Laboratory, University of California, Berkeley, California, USA.
authors: Michael A
authors: MA
authors: Balamotis
authors: Nele
authors: N
authors: Tamberg
authors: Young Jae
authors: YJ
authors: Woo
authors: Jingchuan
authors: J
authors: Li
authors: Brian
authors: B
authors: Davy
authors: Terumi
authors: T
authors: Kohwi-Shigematsu
authors: Yoshinori
authors: Y
authors: Kohwi
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D017781:Genes, Immediate-Early; D056426:Genetic Loci; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism
chemical_list: D036961:Matrix Attachment Region Binding Proteins; C501473:SATB2 protein, mouse; C469541:Satb1 protein, mouse; D014157:Transcription Factors; D004247:DNA