Developmental expression of the SRF co‐activator MAL in brain: role in regulating dendritic morphology

• Published in: Journal of neurochemistry Vol. 98; no. 6; pp. 1778 - 1788
• Main Authors: Shiota, Jun, Ishikawa, Mitsuru, Sakagami, Hiroyuki, Tsuda, Masaaki, Baraban, Jay M., Tabuchi, Akiko
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2006; Blackwell
• Subjects: Animals; Biochemistry and metabolism; Biological and medical sciences; Brain; Brain - drug effects; Brain - embryology; Brain - growth & development; Brain - metabolism; Brain - ultrastructure; Cell culture; Central nervous system; Cerebral Cortex - cytology; cortical neuron; Dendrites - metabolism; Dendrites - ultrastructure; dendritic morphology; Embryo, Mammalian - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Genes, Dominant; Hematologic and hematopoietic diseases; Intracellular Signaling Peptides and Proteins - physiology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; megakaryocytic acute leukemia; Mice; Mice, Inbred C57BL; Neurons; Neurons - drug effects; Neurons - ultrastructure; NIH 3T3 Cells; Protein Structure, Tertiary - physiology; Ribonucleic acid; RNA; RNA interference; RNA, Small Interfering - pharmacology; serum response factor; Signal transduction; Tissue Distribution; Vertebrates: nervous system and sense organs; cortical neuron; Cerebral cortex; RNA interference; Transcription; Central nervous system; Encephalon; Myeloproliferative syndrome; Signal transduction; Actin; Dynamics; Serum; Localization; megakaryocytic acute leukemia; Acute; Rodentia; Acute leukemia; Malignant hemopathy; dendritic morphology; Vertebrata; Mammalia; Megakaryocytic leukemia; Neuron; Mouse; Morphology; Cytoskeleton; serum response factor; Hippocampus
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.03992.x

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.