A CaMKII-NeuroD Signaling Pathway Specifies Dendritic Morphogenesis

Abstract

The elaboration of dendrites is fundamental to the establishment of neuronal polarity and connectivity, but the mechanisms that underlie dendritic morphogenesis are poorly understood. We found that the genetic knockdown of the transcription factor NeuroD in primary granule neurons including in organotypic cerebellar slices profoundly impaired the generation and maintenance of dendrites while sparing the development of axons. We also found that NeuroD mediated neuronal activity-dependent dendritogenesis. The activity-induced protein kinase CaMKII catalyzed the phosphorylation of NeuroD at distinct sites, including endogenous NeuroD at Ser336 in primary neurons, and thereby stimulated dendritic growth. These findings uncover an essential function for NeuroD in granule neuron dendritic morphogenesis. Our study also defines the CaMKII-NeuroD signaling pathway as a novel mechanism underlying activity-regulated dendritic growth that may play important roles in the developing and mature brain.

c-Jun NH2-terminal Kinase (JNK)-interacting Protein-3 (JIP3) Regulates Neuronal Axon Elongation in a Kinesin- and JNK-dependent Manner

“…Neurons were electroporated with various constructs in a Nucleofector device (Amaxa Biosystems), according to the manufacturer's instructions, before plating. To diminish the possibility that the morphological phenotypes observed with the constructs of interest were attributable to their effects on neuronal survival, an expression plasmid for the antiapoptotic protein gene Bcl-xL, which has been reported to have no effect on axon or dendrite morphology in neurons, was co-transfected (17,18).…”

FoxO6 regulates memory consolidation and synaptic function

“…In all transfections, the anti-apoptotic protein Bcl-xl was coexpressed to rule out potential effects of cell survival on neuronal morphology. The expression of Bcl-xl had no effect on the morphology of neurons (Gaudilliere et al 2004;de la Torre-Ubieta et al 2010). Individual images of GFP-labeled DIV5 primary hippocampal neurons prepared from FoxO6 mutant or wild-type mice were captured in a blinded manner on a Nikon eclipse TE2000 epifluorescence microscope using a digital CCD camera (Diagnostic Instruments).…”

Transcriptional and Epigenetic Regulation in Injury-Mediated Neuronal Dendritic Plasticity

“…Evidence suggests that the basic helix-loop-helix transcription factors neurogenin-2 and NeuroD affect dendritic morphological organization in cortical pyramidal neurons and granule neurons, respectively [30][31][32]. Others, such as activating transcription factor-3 (ATF-3) and signal transduction and transcription-3 (STAT3) are better characterized and induce a variety of responses in neurons during development and in response to injury and treatment.…”