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Abstract Background The small non-coding microRNAs play an important role in development by regulating protein translation, but their involvement in axon guidance is unknown. Here, we investigated the role of microRNA-134 (miR-134) in chemotropic guidance of nerve growth cones. Results We found that miR-134 is highly expressed in the neural tube of Xenopus embryos. Fluorescent in situ hybridization also showed that miR-134 is enriched in the growth cones of Xenopus spinal neurons in culture. Importantly, overexpression of miR-134 mimics or antisense inhibitors blocked protein synthesis (PS)-dependent attractive responses of Xenopus growth cones to a gradient of brain-derived neurotrophic factor (BDNF). However, miR-134 mimics or inhibitors had no effect on PS-independent bidirectional responses of Xenopus growth cones to bone morphogenic protein 7 (BMP7). Our data further showed that Xenopus LIM kinase 1 (Xlimk1) mRNA is a potential target of miR-134 regulation. Conclusions These findings demonstrate a role for miR-134 in translation-dependent guidance of nerve growth cones. Different guidance cues may act through distinct signaling pathways to elicit PS-dependent and -independent mechanisms to steer growth cones in response to a wide array of spatiotemporal cues during development.

Abstract Uncovering the mechanisms that regulate dendritic spine morphology has been limited, in part, by the lack of efficient and unbiased methods for analyzing spines. Here, we describe an automated 3D spine morphometry method and its application to spine remodeling in live neurons and spine abnormalities in a disease model. We anticipate that this approach will advance studies of synapse structure and function in brain development, plasticity, and disease.

Abstract Background Cultured spinal motor neurons are a valuable tool to study basic mechanisms of development, axon growth and pathfinding, and, importantly, to analyze the pathomechanisms underlying motor neuron diseases. However, the application of this cell culture model is limited by the lack of efficient gene transfer techniques which are available for other neurons. To address this problem, we have established magnetofection as a novel method for the simple and efficient transfection of mouse embryonic motor neurons. This technique allows for the study of the effects of gene expression and silencing on the development and survival of motor neurons. Results We found that magnetofection, a novel transfection technology based on the delivery of DNA-coated magnetic nanobeads, can be used to transfect primary motor neurons. Therefore, in order to use this method as a new tool for studying the localization and transport of axonal proteins, we optimized conditions and determined parameters for efficient transfection rates of >45% while minimizing toxic effects on survival and morphology. To demonstrate the potential of this method, we have used transfection with plasmids encoding fluorescent fusion-proteins to show for the first time that the spinal muscular atrophy-disease protein Smn is actively transported along axons of live primary motor neurons, supporting an axon-specific role for Smn that is different from its canonical function in mRNA splicing. We were also able to show the suitability of magnetofection for gene knockdown with shRNA-based constructs by significantly reducing Smn levels in both cell bodies and axons, opening new opportunities for the study of the function of axonal proteins in motor neurons. Conclusions In this study we have established an optimized magnetofection protocol as a novel transfection method for primary motor neurons that is simple, efficient and non-toxic. We anticipate that this novel approach will have a broad applicability in the study of motor neuron development, axonal trafficking, and molecular mechanisms of motor neuron diseases.

Background: 3q29 deletion syndrome is associated with a range of medical, neurodevelopmental, and psychiatric phenotypes. The deletion is usually de novo but cases have been reported where the deletion is inherited from apparently unaffected parents. The presence of these unaffected or mildly affected individuals suggests there may be an ascertainment bias for severely affected cases of 3q29 deletion syndrome, thus the more deleterious consequence of the 3q29 deletion may be overestimated. However, a substantial fraction of 3q29 deletion syndrome morbidity is due to psychiatric illness. In many case reports, probands and transmitting parents are not systematically evaluated for psychiatric traits. Here we report results from a systematic phenotyping protocol for neurodevelopmental and neuropsychiatric traits applied to all 3q29 deletion carriers in a multiplex family. Case presentation: Through the 3q29 registry at Emory University, a multiplex family was identified where three offspring had a paternally inherited 3q29 deletion. We evaluated all 4 3q29 deletion family members using our previously described standardized, systematic phenotyping protocol. The transmitting parent reported no psychiatric history, however upon evaluation he was discovered to meet criteria for multiple psychiatric diagnoses including previously undiagnosed schizoaffective disorder. All four 3q29 deletion individuals in the pedigree had multiple psychiatric diagnoses that interfered with quality of life and prohibited successful academic and occupational functioning. Cognitive ability for all individuals was average or below average, but within the normal range. Conclusions: This is the first case report of inherited 3q29 deletion syndrome where all affected individuals in the pedigree have been comprehensively and systematically evaluated for neurodevelopmental and psychiatric symptoms, using a standard battery of normed instruments administered by expert clinicians. Our investigation reveals that individuals with 3q29 deletion syndrome may have psychiatric morbidity that is debilitating, but only apparent through specialized evaluation by an expert. In the absence of appropriate evaluation, individuals with 3q29 deletion syndrome may suffer from psychiatric illness but lack avenues for access to care. The individuals evaluated here all have cognition in the normal range alongside multiple psychiatric diagnoses each, suggesting that cognitive ability alone is not a representative proxy for 3q29 deletion-associated disability. These results require replication in a larger cohort of individuals with 3q29 deletion syndrome. [ABSTRACT FROM AUTHOR]

A recent theory about the basis for fragile X syndrome is now validated in a mouse model. The findings point the way to treatment options targeting group 1 metabotropic glutamate [...]

Localization and local translation of mRNA plays a key role in neuronal development and function. While studies in various systems have provided insights into molecular mechanisms of mRNA transport and local protein synthesis, the factors that control the assembly of mRNAs and mRNA binding proteins into messenger ribonucleoprotein (mRNP) transport granules remain largely unknown. In this review we will discuss how insights on a motor neuron disease, spinal muscular atrophy (SMA), is advancing our understanding of regulated assembly of transport competent mRNPs and how defects in their assembly and delivery may contribute to the degeneration of motor neurons observed in SMA and other neurological disorders. [ABSTRACT FROM AUTHOR]