title: MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling.
abstract: Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons.
authors.affiliation: Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE 68198, United States.
authors.forename: Minhan
authors.initials: M
authors.lastname: Ka
authors.affiliation: Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE 68198, United States.
authors.forename: Eui-Man
authors.initials: EM
authors.lastname: Jung
authors.affiliation: Dorris Neuroscience Center and Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, United States.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mueller
authors.affiliation: Developmental Neuroscience, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: wooyang.kim@unmc.edu.
authors.forename: Woo-Yang
authors.initials: WY
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002465:Cell Movement; D018385:Centrosome / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D061251:Primary Cell Culture; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D059008:Time-Lapse Imaging
chemical_list: D007527:Isoenzymes; C490632:Macf1 protein, mouse; D008840:Microfilament Proteins; D049452:Green Fluorescent Proteins; D038362:Glycogen Synthase Kinase 3
keywords: Cytoskeleton; GSK-3; MACF1; Microtubule; Neuronal migration