Defective pruning of hippocampal projections in mouse models of Mecp2 dysfunction

MARIA LAURA BERTOLDI; ALICIA DEGANO

Huerta Grande, Córdoba. Argentina

Congreso; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2012

Sociedad Argentina de Investigación en Neurociencias

Methyl Cytosine Binding Protein 2 (MeCP2) is a transcriptional regulator that binds to methylated DNA. Alterations in the expression levels of this protein have been related to autism spectrum disorders. Current evidence establishes that Mecp2 is important for neuronal maturation, neurite complexity and synaptic plasticity, although the underlying mechanisms remain unknown. Previously, we have shown that Mecp2 dysfunction alters the formation and maturation of the olfactory circuit, and we hypothesized that Mecp2 plays a role in the establishment of neural connectivity. Now we aim to explore the role of this protein in axonal guidance and pruning events in the hippocampus at early postnatal stages. In the present work, we used two different mouse models of Mecp2 dysfunction to analyze the pruning of hippocampal mossy fibers. Our results show a delay in the pruning of these projections in the absence of functional Mecp2. In addition, we detected changes in the expression levels of Class 3 semaphorins, a family of guidance molecules that play an important role in the establishment of neural connectivity. Thus, the present results suggest that Mecp2 plays a role in the development/refinement of neural circuits, possibly by transcriptional regulation of guidance cues expression.