Exploitation of the Bio-MEMORY collection CNR-IBBR-CeLITABASE for the characterization of highly conserved molecular pathways involved in neurodevelopmental disorders (NDD).

Neurodevelopmental disorder (NDD) genes play a role across a range of biological functions, including transcriptional regulation, epigenetic modification, and synaptic structure and functioning. Although NDD genes are functionally diverse, they are highly inter-connected and control multiple processes, including neuronal morphology, synaptic plasticity and neuronal homeostasis. In this framework, the identification of secondary molecular determinants contributing to disease phenotypes is essential for dissecting the pathogenetic mechanisms. The complexity of the intricate disease network underlying NDD pathology requires a reductionist approach and the use of a simplified animal model such as C. elegans offers a particularly suitable tool for understanding the function of highly conserved genes involved in neuronal function. Furthermore, the homology between C. elegans and mammalian genomes, and the fact that several mutant strains are accessible, makes this system ideal for the identification of complex and conserved molecular pathways. Here we report on a multidisciplinary study by using a C. elegans mutant strain collection, available at CNR-IBBR (BioMemory collection CNR-IBBR-CELITABASE), aiming to identify mechanistically conserved interactions among the highly evolutionary conserved ARX/alr-1 gene, which encodes an homeotic bifunctional transcription factor involved in NDD, its direct targets and the related-neuronal functions. Using this approach, we are rapidly identifying several genes simultaneously among a number of conserved NDD targets implicated in specific neuronal features in nematodes, such as mechano-response and GABAergic neuronal maturation. The identification of these genes will allow to probe the highly conserved history of homeotic transcription factors and their pleiotropic nature underlying neuronal network architecture and involved in other NDDs.