Jun Shiota, Mitsuru Ishikawa and Akiko Tabuchi contributed equally to this work.
Developmental expression of the SRF co-activator MAL in brain: role in regulating dendritic morphology
Article first published online: 5 JUL 2006
Journal of Neurochemistry
Volume 98, Issue 6, pages 1778–1788, September 2006
How to Cite
Shiota, J., Ishikawa, M., Sakagami, H., Tsuda, M., Baraban, J. M. and Tabuchi, A. (2006), Developmental expression of the SRF co-activator MAL in brain: role in regulating dendritic morphology. Journal of Neurochemistry, 98: 1778–1788. doi: 10.1111/j.1471-4159.2006.03992.x
- Issue published online: 5 JUL 2006
- Article first published online: 5 JUL 2006
- Received February 10, 2006; revised manuscript received April 29, 2006; accepted May 2, 2006.
- cortical neuron;
- dendritic morphology;
- megakaryocytic acute leukemia;
- RNA interference;
- serum response factor
The dynamic changes in dendritic morphology displayed by developing and mature neurons have stimulated interest in deciphering the signaling pathways involved. Recent studies have identified megakaryocytic acute leukemia (MAL), a serum response factor (SRF) co-activator, as a key component of a signaling pathway linking changes in the actin cytoskeleton to SRF-mediated transcription. To help define the role of this pathway in regulating dendritic morphology, we have characterized the pattern of MAL expression in the developing and adult brain, and have examined its role in regulating dendritic morphology in cultured cortical neurons. In histological studies of mouse brain, we found prominent expression of MAL in neurons in adult hippocampus and cerebral cortex. MAL immunostaining revealed localization of this protein in neuronal cell bodies and apical dendrites. During development, an increase in MAL expression occurs during the second post-natal week. Expression of dominant negative MAL constructs or MAL siRNA in cortical neurons grown in primary culture reduces the number of dendritic processes and decreases the basal level of SRF-mediated transcription. Taken together, these findings indicate that the MAL-SRF signaling pathway plays a key role in regulating dendritic morphology.