title: Soluble guanylate cyclase generation of cGMP regulates migration of MGE neurons.
abstract: 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 α 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 and NOS activity rapidly induces neurite retraction of MGE cells in vitro and in slice culture and robustly inhibits cell migration from the MGE and caudal ganglionic eminence. We provide evidence that these cellular phenotypes are mediated by activation of the Rho signaling pathway and inhibition of myosin light chain phosphatase activity.
authors.affiliation: Department of Psychiatry, Neuroscience Program and the Nina Ireland Laboratory of Developmental Neurobiology, University of California San Francisco, San Francisco, California 94158-2324, Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, and Cold Spring Harbor Laboratories, Laurel Hollow, New York 11791.
authors.forename: Shyamali
authors.initials: S
authors.lastname: Mandal
authors.forename: Amelia
authors.initials: A
authors.lastname: Stanco
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Buys
authors.forename: Grigori
authors.initials: G
authors.lastname: Enikolopov
authors.forename: John L R
authors.initials: JL
authors.lastname: Rubenstein
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism* / Q000502:physiology; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008473:Median Eminence / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D018994:Myosin Light Chains / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000378:metabolism / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071756:Soluble Guanylyl Cyclase; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C088334:Distal-less homeobox proteins; C000605668:Gucy1a3 protein, mouse; D018398:Homeodomain Proteins; C498504:LHX6 protein, mouse; D060850:LIM-Homeodomain Proteins; D018994:Myosin Light Chains; D009419:Nerve Tissue Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP