Developmental expression of the SRF co-activator MAL in brain: Role in regulating dendritic morphology

Jun Shiota, Mitsuru Ishikawa, Hiroyuki Sakagami, Masaaki Tsuda, Jay M. Baraban, Akiko Tabuchi

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1778-1788
Number of pages11
JournalJournal of Neurochemistry
Volume98
Issue number6
DOIs
StatePublished - Sep 2006
Externally publishedYes

Keywords

  • Cortical neuron
  • Dendritic morphology
  • Megakaryocytic acute leukemia
  • RNA interference
  • Serum response factor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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