NOVA2-mediated RNA regulation is required for axonal pathfinding during development.

The neuron specific RNA-binding proteins NOVA1 and NOVA2 are highly homologous alternative splicing regulators. NOVA proteins regulate at least 700 alternative splicing events in vivo, yet relatively little is known about the biologic consequences of NOVA action and in particular about functional differences between NOVA1 and NOVA2. Transcriptome-wide searches for isoform-specific functions, using NOVA1 and NOVA2 specific HITS-CLIP and RNA-seq data from mouse cortex lacking either NOVA isoform, reveals that NOVA2 uniquely regulates alternative splicing events of a series of axon guidance related genes during cortical development. Corresponding axonal pathfinding defects were specific to NOVA2 deficiency: Nova2-/- but not Nova1-/- mice had agenesis of the corpus callosum, and axonal outgrowth defects specific to ventral motoneuron axons and efferent innervation of the cochlea. Thus we have discovered that NOVA2 uniquely regulates alternative splicing of a coordinate set of transcripts encoding key components in cortical, brainstem and spinal axon guidance/outgrowth pathways during neural differentiation, with severe functional consequences in vivo

A spike-timing-dependent plasticity rule for dendritic spines

The structural organization of excitatory inputs supporting spike-timing-dependent plasticity (STDP) in dendritic spines remains unknown. Using a spine STDP protocol, the authors uncover the STDP rules for single, clustered and distributed dendritic spines in the basal dendrites of layer 5 pyramidal neurons in juvenile mice

Evolution of dopamine receptors: phylogenetic evidence suggests a later origin of the DRD2l and DRD4rs dopamine receptor gene lineages

Dopamine receptors are integral membrane proteins whose endogenous ligand is dopamine. They play a fundamental role in the central nervous system and dysfunction of dopaminergic neurotransmission is responsible for the generation of a variety of neuropsychiatric disorders. From an evolutionary standpoint, phylogenetic relationships among the DRD1 class of dopamine receptors are still a matter of debate as in the literature different tree topologies have been proposed. In contrast, phylogenetic relationships among the DRD2 group of receptors are well understood. Understanding the time of origin of the different dopamine receptors is also an issue that needs further study, especially for the genes that have restricted phyletic distributions (e.g., DRD2l and DRD4rs). Thus, the goal of this study was to investigate the evolution of dopamine receptors, with emphasis on shedding light on the phylogenetic relationships among the D1 class of dopamine receptors and the time of origin of the DRD2l and DRD4rs gene lineages. Our results recovered the monophyly of the two groups of dopamine receptors. Within the DRD1 group the monophyly of each paralog was recovered with strong support, and phylogenetic relationships among them were well resolved. Within the DRD1 class of dopamine receptors we recovered the sister group relationship between the DRD1C and DRD1E, and this clade was recovered sister to a cyclostome sequence. The DRD1 clade was recovered sister to the aforementioned clade, and the group containing DRD5 receptors was sister to all other DRD1 paralogs. In agreement with the literature, among the DRD2 class of receptors, DRD2 was recovered sister to DRD3, whereas DRD4 was sister to the DRD2/DRD3 clade. According to our phylogenetic tree, the DRD2l and DRD4rs gene lineages would have originated in the ancestor of gnathostomes between 615 and 473 mya. Conservation of sequences required for dopaminergic neurotransmission and small changes in regulatory regions suggest a functional refinement of the dopaminergic pathways along evolution

Figure source data for "Altered integration of excitatory inputs onto the basal dendrites of layer 5 pyramidal neurons in a mouse model of Fragile X syndrome"

Figure source data for "Altered integration of excitatory inputs onto the basal dendrites of layer 5 pyramidal neurons in a mouse model of Fragile X syndrome" * D.E.M & S.M.-R. contributed equally to this work</p