MAPK-upstream protein kinase (MUK) regulates the radial migration of immature neurons in telencephalon of mouse embryo.
The radial migration of differentiating neurons provides an essential step in the generation of laminated neocortex, although its molecular mechanism is not fully understood. We show that the protein levels of a JNK activator kinase, MUK/DLK/ZPK, and JNK activity increase potently and temporally in newly generated neurons in developing mouse telencephalon during radial migration. The ectopic expression of MUK/DLK/ZPK in neural precursor cells in utero impairs radial migration, whereas it allows these cells to leave the ventricular zone and differentiate into neural cells. The MUK/DLK/ZPK protein is associated with dotted structures that are frequently located along microtubules and with Golgi apparatus in cultured embryonic cortical cells. In COS-1 cells, MUK/DLK/ZPK overexpression impairs the radial organization of microtubules without massive depolymerization. These results suggest that MUK/DLK/ZPK and JNK regulate radial cell migration via microtubule-based events.
Hirai
Syu-ichi
S
Department of Molecular Biology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. sh3312@med.yokohama-cu.ac.jp
Kawaguchi
Atsumi
A
Hirasawa
Ryutaro
R
Baba
Masaya
M
Ohnishi
Tetsuo
T
Ohno
Shigeo
S
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000502:physiology*; D002522:Chlorocebus aethiops; D015870:Gene Expression; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008870:Microtubules / Q000502:physiology; D048055:Mitogen-Activated Protein Kinase 8; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019579:Neocortex / Q000196:embryology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013687:Telencephalon / Q000166:cytology*
D011993:Recombinant Fusion Proteins; D048056:Mitogen-Activated Protein Kinase 9; D017346:Protein Serine-Threonine Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12