Satb1 Ablation Alters Temporal Expression of Immediate Early Genes and Reduces Dendritic Spine Density during Postnatal Brain Development

Michael A. Balamotisa Lawrence Berkeley National Laboratory, University of California, Berkeley, California, USA

Nele Tamberga Lawrence Berkeley National Laboratory, University of California, Berkeley, California, USA;b Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia

Young Jae Wooa Lawrence Berkeley National Laboratory, University of California, Berkeley, California, USA

Jingchuan Lia Lawrence Berkeley National Laboratory, University of California, Berkeley, California, USA

Brian Davya Lawrence Berkeley National Laboratory, University of California, Berkeley, California, USA

Terumi Kohwi-Shigematsua Lawrence Berkeley National Laboratory, University of California, Berkeley, California, USACorrespondence[email protected] [email protected]

Yoshinori Kohwia Lawrence Berkeley National Laboratory, University of California, Berkeley, California, USACorrespondence[email protected] [email protected]

show all

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.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.05917-11.

ACKNOWLEDGMENTS

This work was supported by NIH-RO1 (CA39681 and GM63026; to T.K.-S.) and NIH-RO1 (NS41128; to Y.K.) and by the Director, Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy under contract no. DE-AC02-05CH11231.

We especially appreciate the critical review and constructive suggestions for the manuscript provided by Rui Galvao and Minoree Kohwi. We thank Shutao Cai for his help in brain ChIP analysis. We are also grateful to S. A. Regmi, E. Peiffer, undergraduate students from UC Berkeley (B. Dang, U. Awan, J. Yoon, K. Kothandapani, M. Jen, D. Eum, and M. Lobo), and M. Miyano for technical assistance and mouse care. We thank Kevin Peet for editorial assistance.

Satb1 Ablation Alters Temporal Expression of Immediate Early Genes and Reduces Dendritic Spine Density during Postnatal Brain Development

Information for

Open access

Opportunities

Help and information

Satb1 Ablation Alters Temporal Expression of Immediate Early Genes and Reduces Dendritic Spine Density during Postnatal Brain Development

Abstract

SUPPLEMENTAL MATERIAL

ACKNOWLEDGMENTS

Related research

To cite this article:

Download citation

Information for

Open access

Opportunities

Help and information

Keep up to date

Your download is now in progress and you may close this window

Login or register to access this feature