title: A role for mDia, a Rho-regulated actin nucleator, in tangential migration of interneuron precursors.
abstract: In brain development, distinct types of migration, radial migration and tangential migration, are shown by excitatory and inhibitory neurons, respectively. Whether these two types of migration operate by similar cellular mechanisms remains unclear. We examined neuronal migration in mice deficient in mDia1 (also known as Diap1) and mDia3 (also known as Diap2), which encode the Rho-regulated actin nucleators mammalian diaphanous homolog 1 (mDia1) and mDia3. mDia deficiency impaired tangential migration of cortical and olfactory inhibitory interneurons, whereas radial migration and consequent layer formation of cortical excitatory neurons were unaffected. mDia-deficient neuroblasts exhibited reduced separation of the centrosome from the nucleus and retarded nuclear translocation. Concomitantly, anterograde F-actin movement and F-actin condensation at the rear, which occur during centrosomal and nuclear movement of wild-type cells, respectively, were impaired in mDia-deficient neuroblasts. Blockade of Rho-associated protein kinase (ROCK), which regulates myosin II, also impaired nuclear translocation. These results suggest that Rho signaling via mDia and ROCK critically regulates nuclear translocation through F-actin dynamics in tangential migration, whereas this mechanism is dispensable in radial migration.
authors.affiliation: Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Shinohara
authors.forename: Dean
authors.initials: D
authors.lastname: Thumkeo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamijo
authors.forename: Naoko
authors.initials: N
authors.lastname: Kaneko
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Sawamoto
authors.forename: Keisuke
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hirohide
authors.initials: H
authors.lastname: Takebayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Ishizaki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Furuyashiki
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
mesh_terms: D000199:Actins / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D003857:Deoxyuridine / Q000031:analogs & derivatives; D000089622:Doublecortin Domain Proteins; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000080865:Formins; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D005829:Geniculate Bodies / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D005968:Glutamate Decarboxylase / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D007395:Interneurons / Q000502:physiology*; D020547:Lateral Ventricles / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009924:Organ Culture Techniques; D010320:Parvalbumins / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D000091042:Reelin Protein; D012097:Repressor Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D000577:Amides; C511143:Bcl11b protein, mouse; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; C000624101:Cux1 protein, mouse; C491464:Diap1 protein, mouse; C491463:Diap2 protein, mouse; D000089622:Doublecortin Domain Proteins; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D051858:Forkhead Transcription Factors; D000080865:Formins; C432918:Foxp2 protein, mouse; D018398:Homeodomain Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D010320:Parvalbumins; D011725:Pyridines; D000091042:Reelin Protein; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C485184:enhanced green fluorescent protein; C108830:Y 27632; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D054460:rho-Associated Kinases; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine