In marked contrast to the overwhelming research progress achieved for common neurological pathologies, rare neurodevelopmental diseases displaying a early-onset neurodegenerative spectrum remain poorly investigated, leaving patients diagnostic and therapeutic care needs unmet. The work carried under this MSCA project contributed to generating a fast cross-disciplinary in vivo workflow for functional genomics that will be exploited beyond the diseases examined here. Bringing comparative embryology and neurobiology expertise to a hospital-type of research setting, the work has validated and investigated mechanistically the impact of genetic alterations recently identified in a group of patients with infantile neurodegeneration. Addressing the specifics of the pathological mechanisms and sharing the results offers differential diagnosis tools and stimulate the search for targeted cure. Adding to recent reports for a similar condition, we are among the first to clarify defective spinal motoneurons development and homeostasis as a major disease sign, which was so far hypothesized, maifested before the onset of locomotor disabilities. We began to correlate genotypes to phenotypes, showing a dosage effect in an organismal context, that provides insights to explain progressive motor deterioration. The data ultimately contribute to inform diagnosis with respect to life quality and therapeutic prospective. We expect to finalize soon the data collection for the preliminarily characterization of the stable zebrafish model of disease and for peer review publication. These will be made available within the scientific community for further exploitation, open-end hypothesis testing and drug screening.
