The Role of Dock7 in Neuromuscular Health and Function

Dedicator of cytokinesis (DOCK) proteins have critical roles in myoblast fusion, glucose metabolism, skeletal muscle regeneration, and neuronal polarity. Previously, we demonstrated that DOCK3 is a dosage-sensitive modifier of Duchenne muscular dystrophy (DMD) pathologies as DOCK3 expression was induced in response to dystrophic disease progression. Following a similar pattern, DOCK7 expression is upregulated in both human DMD muscle and multiple DMD mouse models. DOCK7 primarily activates a RAC1 signaling cascade that functions to modulate cytoskeletal actin-filament polymerization and organization. DOCK7 deficiency leads to hypotonia and ataxia. We hypothesized that DOCK7 plays an integral role in neuromuscular health and function through its activation of RAC1 signaling. The goal of this sequencing experiment is to determine whether Dock7 function is critical to skeletal muscle, motor neurons or both.