Soluble guanylate cyclase generation of cGMP regulates migration of MGE neurons

Here we have provided evidence that nitric oxide-cyclic GMP (NO-cGMP) signaling regulates neurite length and migration of immature neurons derived from the medial ganglionic eminence (MGE). Dlx1/2^-/- and Lhx6^-/- mouse mutants, which exhibit MGE interneuron migration defects, have reduced expression of the gene encoding the - subunit of a soluble guanylate cyclase (Gucy1A3). Furthermore, Dlx1/2^-/- mouse mutants have reduced expression of NO synthase 1 (NOS1). Gucy1A3^-/- mice have a transient reduction in cortical interneuron number. Pharmacological inhibition of soluble guanylate cyclase andNOSactivity rapidly induces neurite retraction ofMGE cells in vitro and in slice culture and robustly inhibits cell migration from theMGEand caudal ganglionic eminence.Weprovide evidence that these cellular phenotypes are mediated by activation of the Rho signaling pathway and inhibition of myosin light chain phosphatase activity.