Genetics of mirror movements identifies a multifunctional complex required for Netrin-1 guidance and lateralization of motor control

• DOI: 10.1126/sciadv.add5501
• Publication Date: 2023-05-12T17:58:26Z
• Authors: Sabrina Schlienger; Patricia T. Yam; Nursen Balekoglu; Hugo Ducuing; Jean-Francois Mic...; Shirin Makihara; Daniel K. Kramer; Baoyu Chen; Alfonso Fasano; Alfredo Berardelli; Fadi F. Hamdan; Guy A. Rouleau; Myriam Srour; Frederic Charron
• Keywords: Netrin; Slit; Commissure

Mirror movements (MM) disorder is characterized by involuntary on one side of the body that mirror intentional opposite side. We performed genetic characterization a family with autosomal dominant MM and identified ARHGEF7, RhoGEF, as candidate gene. found Arhgef7 its partner Git1 bind directly to Dcc. Dcc receptor for Netrin-1, an axon guidance cue attracts commissural axons midline, promoting midline crossing tracts. show are required Netrin-1-mediated act multifunctional effector complex. Arhgef7/Git1 activates Rac1 Cdc42 inhibits Arf1 downstream Netrin-1. Furthermore, Arhgef7/Git1, via Arf1, mediates Netrin-1-induced increase in cell surface Mice heterozygous have defects trajectories increased symmetrical paw placements during skilled walking, MM-like phenotype. Thus, we delineated how ARHGEF7 mutation causes MM.