Dyrk1A Influences Neuronal Morphogenesis Through Regulation of Cytoskeletal Dynamics in Mammalian Cortical Neurons

Down syndrome (DS) is the most frequent genetic cause of mental retardation. Cognitive dysfunction in these patients is correlated with reduced dendritic branching and complexity, along with fewer spines of abnormal shape that characterize the cortical neuronal profile of DS. DS phenotypes are caused by the disruptive effect of specific trisomic genes. Here, we report that overexpression of dual-specificity tyrosine phosphorylation-regulated kinase 1A, DYRK1A, is sufficient to produce the dendritic alterations observed in DS patients. Engineered changes in Dyrk1A gene dosage in vivo strongly alter the postnatal dendritic arborization processes with a similar progression than in humans. In cultured mammalian cortical neurons, we determined a reduction of neurite outgrowth and synaptogenesis. The mechanism underlying neurite dysgenesia involves changes in the dynamic reorganization of the cytoskeleton.

Developmental Expression of Kv Potassium Channels at the Axon Initial Segment of Cultured Hippocampal Neurons

Axonal outgrowth and the formation of the axon initial segment (AIS) are early events in the acquisition of neuronal polarity. The AIS is characterized by a high concentration of voltage-dependent sodium and potassium channels. However, the specific ion channel subunits present and their precise localization in this axonal subdomain vary both during development and among the types of neurons, probably determining their firing characteristics in response to stimulation. Here, we characterize the developmental expression of different subfamilies of voltage-gated potassium channels in the AISs of cultured mouse hippocampal neurons, including subunits Kv1.2, Kv2.2 and Kv7.2. In contrast to the early appearance of voltage-gated sodium channels and the Kv7.2 subunit at the AIS, Kv1.2 and Kv2.2 subunits were tethered at the AIS only after 10 days in vitro. Interestingly, we observed different patterns of Kv1.2 and Kv2.2 subunit expression, with each confined to distinct neuronal populations. The accumulation of Kv1.2 and Kv2.2 subunits at the AIS was dependent on ankyrin G tethering, it was not affected by disruption of the actin cytoskeleton and it was resistant to detergent extraction, as described previously for other AIS proteins. This distribution of potassium channels in the AIS further emphasizes the heterogeneity of this structure in different neuronal populations, as proposed previously, and suggests corresponding differences in action potential regulation.

COST Action Urban Agriculture Europe Training School «Urban agriculture inside the city:alternatives for vacant lots and public space»

The third Training School of the Action took place in Vitoria-Gasteiz (Basque country, Spain) from 24th to 26th September 2014. Vitoria-Gateiz has experimented an important urban outgrowth in the last decade, mainly through the planning and development of two new neighborhoods, Zabalgana and Salburúa, situated at the eastern and western border of the city, by the Greenbelt. These new development are well-equipped and designed according to sustainability principles. Nevertheless, among the main problems they present is their over-dimensioned public space, which creates some areas lacking enough density and mix of uses. On the other hand it is very expensive for the municipality to maintain these public space with the high Vitorian urban standards for public space. The proposed solution for this problem is a strategy of "re-densification" through the insertion of new uses The debate has arisen about which are the most adequate uses to insert in order to get an increasing of urban vitality, specially considering that housing has reached its peak and that Vitoria-Gasteiz is well served with social and sport amenities. The main goal of the TS was to offer an opportunity for the reflection about how urban agriculture might be an optimal alternative for the re-qualifying of this over-dimensioned public space in the new neighbourhoods, especially considering it synergic potential as a tool for production, leisure and landscaping, including the possibility of energy crops within the limits of urban space. Continuity with rural and natural surrounding area through alternatives for urban fringe at the small scale is a relevant issue to be considered as well within the reflection. Taking Zabalgana neighbourhood as a practical field for experiment, the Training School is conceived as a practical and intensive design charrette to be held during a whole day after two days of local knowledge-deepening through field visits and presentations.