Final Report Summary - SYNSCAFF (Synaptic scaffolding proteins orchestrating cortical synapse organisation during development)
The development of neural circuitry is a complex process, and the role of many of its components - notably the control of neuronal morphology, the formation of specific synaptic connections as well as the exquisite localisation of key synaptic proteins - is still very poorly understood. This represents the starting scenario for the SYNSCAFF project who aimed at reaching a more comprehensive understanding of cortical networking during development and in particular of genes and their products governing the complex molecular mechanisms driving synaptic structuring and organisation during development of cortical networks and circuitries. This project integrated the information about the role of different candidate genes / proteins in synaptic formation, remodelling and function and it capitalises on results obtained in in vitro systems and translated them to increase our knowledge on mental retardation, identifying both key steps responsible for defect of development and new genes / proteins and mechanisms responsible for a defect in development.
The final goal to 'define the molecular portrait of cortical synapse during development, defining the key localisation of gene products within the synaptic structure' was accomplished. In fact, the SYNSCAFF consortium had the capability to characterise gene products responsible for synapse formation, addressing the role of both presynaptic proteins and postsynaptic ones. Further, we identified and localised in defined synaptic domains new proteins involved in synaptic formation, analysed their role in synaptic function in vitro and by means of adequate animal models.
The impact of mutation of key genes ruling excitatory synaptic function in mental retardation was also addressed. Transgenic animals for scaffolding proteins as well as for key elements in mental retardation were characterised in great molecular, functional and behavioural details, reflecting the transferability of results obtained in in vitro systems. Animal model for mutated scaffolds, i.e. Bassoon ko mice, were clearly identified and characterised for molecular electrophysiological and behavioural aspects.
The key results of the consortium have been further exploited by Biotest, who designed and produced new antibodies for proteins analysed by the consortium, thus defining new tools that will be now available to the scientific community. The scientific contribution of SYNSCAFF to the knowledge on assembly and function of the excitatory synapse, can be appreciated and deducted by the following schemes; the first one represents the current knowledge on excitatory synaptic structure at the start of our project, whilst the second one reflects the actual knowledge implemented by the recent findings of our consortium.
The strong scientific value of SYNSCAFF and its strong impact on the scientific community is more evidently assessed by the high number of publications arising from the consortium: 42 accepted papers in peer review journals, 11 manuscripts submitted and in preparation. These results represent the major outcome of SYNSCAFF and testify the dissemination capability of the consortium.
The final goal to 'define the molecular portrait of cortical synapse during development, defining the key localisation of gene products within the synaptic structure' was accomplished. In fact, the SYNSCAFF consortium had the capability to characterise gene products responsible for synapse formation, addressing the role of both presynaptic proteins and postsynaptic ones. Further, we identified and localised in defined synaptic domains new proteins involved in synaptic formation, analysed their role in synaptic function in vitro and by means of adequate animal models.
The impact of mutation of key genes ruling excitatory synaptic function in mental retardation was also addressed. Transgenic animals for scaffolding proteins as well as for key elements in mental retardation were characterised in great molecular, functional and behavioural details, reflecting the transferability of results obtained in in vitro systems. Animal model for mutated scaffolds, i.e. Bassoon ko mice, were clearly identified and characterised for molecular electrophysiological and behavioural aspects.
The key results of the consortium have been further exploited by Biotest, who designed and produced new antibodies for proteins analysed by the consortium, thus defining new tools that will be now available to the scientific community. The scientific contribution of SYNSCAFF to the knowledge on assembly and function of the excitatory synapse, can be appreciated and deducted by the following schemes; the first one represents the current knowledge on excitatory synaptic structure at the start of our project, whilst the second one reflects the actual knowledge implemented by the recent findings of our consortium.
The strong scientific value of SYNSCAFF and its strong impact on the scientific community is more evidently assessed by the high number of publications arising from the consortium: 42 accepted papers in peer review journals, 11 manuscripts submitted and in preparation. These results represent the major outcome of SYNSCAFF and testify the dissemination capability of the consortium.
