Via Luigi Vanvitelli 32
Cellular and molecular mechanisms of synapse development
The proper assembly and function of neural circuits require synaptic excitation and inhibition to be tightly balanced. The impairment of such equilibrium determines different pathological conditions such as autism spectrum disorders, intellectual disability, epilepsy and schizophrenia.
The correct ratio of excitatory and inhibitory synapses (E/I ratio) and their relative distribution are attained in the early stages of brain development suggesting the existence of developmental mechanisms able to coordinate synaptogenesis and to set the equilibrium between the number of excitatory and inhibitory synapses. At present, very little is known regarding the genes and the molecular pathways involved in these mechanisms.
My research activity is focused on 1) investigating the cellular and molecular mechanisms involved in synapse formation in vivo and coordinating the E/I balance during brain development; 2) understanding how defects in synaptic proteins disrupt the E/I ratio and lead to failure of neuronal homeostasis.
To this aim, we are deploying several techniques ranging from single cell manipulation of gene function in vivo (in utero electroporation combined with genome-editing techniques) to biochemical and super-resolution imaging approaches (STED, Stimulated Emission Depletion microscopy).
In conclusion, the main goal of my research is to unravel new cellular and molecular mechanisms of synapse development and provide new insights into potential pharmacological targets for treating neurodevelopmental disorders.
Representative selected publications
- Fossati M, Pizzarelli R, Schmidt ER, Kupferman JV, Stroebel D, Polleux F, Charrier C. (2016) “SRGAP2 and Its Human-Specific Paralog Co-Regulate the Development of Excitatory and Inhibitory Synapses” Neuron 2016 Jun 29. pii: S0896-6273(16)30266-5. doi: 10.1016/j.neuron.2016.06.013
- Fossati M., Colombo S.F. and Borgese N. (2014) “A positive signal prevents secretory membrane cargo from recycling between the Golgi and the ER” EMBO J. 2014 Sep17;33(18):2080-97; doi: 10.15252/embj.201488367 Article recommended in F1000 Prime
- Fossati M., Goud B., Borgese N. and Manneville JB. (2014) “An investigation of the effect of membrane curvature on transmembrane-domain dependent protein sorting in lipid bilayers” Cell Logist. 2014 May;4:e29087; doi:10.4161/cl.29087
- Fossati M., Borgese N., Colombo S.F. and Francolini M. (2014) “Visualization of endoplasmic reticulum sub-domains in cultured cells” J. Vis. Exp. 2014 Feb 18;(84):e50985. doi: 10.3791/50985
- Fasana E., Fossati M., Brambillasca S., Francolini M. and Borgese N. (2010) “A VAP-B mutant linked to Amyotrophic Lateral Sclerosis generates a novel form of Organized Smooth Endoplasmic Reticulum” FASEB J. 2010 May;24(5):1419-30. doi: 10.1096/fj.09-147850