Neurodevelopmental disorders (NDD) such as autism spectrum disorders, X-linked mental retardation, and syndromic/non-syndromic intellectual disabilities are diseases characterized by motor and learning deficits. These pathologies affect about 2% of the world population and can be caused by gene mutations and influenced by environmental factors. Chromatin modifications play a fundamental role during brain development and in particular histone lysine methylation genes are often found mutated in patients with NDD. However how these mutations affect neuronal development is still unclear.
set-2 encodes for a lysine methyltransferase (KMT) that is part of the COMPASS complex and is the main responsible for the di- and tri-methylation of H3K4 in C.elegans. Loss of
set-2 results in axon guidance defects, also observed in mutants for the components of the COMPASS complex, suggesting that
set-2 acts in the context of the complex to regulate axon pathfinding. Using genetic interaction analyses, we show that
set-2, together with other H3K4 regulators, acts trough the regulation of
wsp-1, a gene involved in actin remodeling. Future experiments will be focused to understand the molecular mechanism by which
set-2 regulates
wsp-1 and how loss of
set-2 affects neuronal development and behavior.