The cellular roles of the lissencephaly gene LIS1, and what they tell us about brain development.

Lissencephaly is a severe brain developmental disease characterized by mislocalization of cortical neurons. This class of diseases has received considerable recent attention for their promise in shedding light on the mechanisms underlying the massive waves of neural progenitor cell migration required for brain development. Classical lissencephaly results from sporadic mutations in the human LIS1 gene, which has been implicated in regulating the microtubule motor protein cytoplasmic dynein. This connection supports a role for LIS1 in cell motility, and suggests that defects in dyneinmediated movement are responsible for lissencephaly. This article reviews evidence regarding the cellular defects contributing to classical lissencephaly, with emphasis on recent live analysis of LIS1-deficient neural progenitor cell motility in brain tissue.

[1]  R. Vallee,et al.  Role of the kinetochore/cell cycle checkpoint protein ZW10 in interphase cytoplasmic dynein function , 2006, The Journal of cell biology.

[2]  A. Musacchio,et al.  Regulation of Cytoplasmic Dynein ATPase by Lis1 , 2006, The Journal of Neuroscience.

[3]  M. Götz,et al.  Developmental cell biology: The cell biology of neurogenesis , 2005, Nature Reviews Molecular Cell Biology.

[4]  S. Mcconnell,et al.  Cytoskeletal coordination during neuronal migration. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[5]  A. Kriegstein,et al.  LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages , 2005, The Journal of cell biology.

[6]  Michel Bornens,et al.  Nucleokinesis in Tangentially Migrating Neurons Comprises Two Alternating Phases: Forward Migration of the Golgi/Centrosome Associated with Centrosome Splitting and Myosin Contraction at the Rear , 2005, The Journal of Neuroscience.

[7]  R. Vallee,et al.  How dynein helps the cell find its center: a servomechanical model. , 2005, Trends in cell biology.

[8]  G. Gundersen,et al.  Nuclear Movement Regulated by Cdc42, MRCK, Myosin, and Actin Flow Establishes MTOC Polarization in Migrating Cells , 2005, Cell.

[9]  L. Tsai,et al.  Ndel1 Operates in a Common Pathway with LIS1 and Cytoplasmic Dynein to Regulate Cortical Neuronal Positioning , 2004, Neuron.

[10]  M. Hatten,et al.  Par6α signaling controls glial-guided neuronal migration , 2004, Nature Neuroscience.

[11]  Arnold R Kriegstein,et al.  Patterns of neuronal migration in the embryonic cortex , 2004, Trends in Neurosciences.

[12]  A. Wynshaw-Boris,et al.  Lis1 and doublecortin function with dynein to mediate coupling of the nucleus to the centrosome in neuronal migration , 2004, The Journal of cell biology.

[13]  Y. Terada,et al.  Interaction of Cep135 with a p50 dynactin subunit in mammalian centrosomes. , 2004, Cell motility and the cytoskeleton.

[14]  Xiumin Yan,et al.  Nudel functions in membrane traffic mainly through association with Lis1 and cytoplasmic dynein , 2004, The Journal of cell biology.

[15]  A. Kriegstein,et al.  Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases , 2004, Nature Neuroscience.

[16]  R. Vallee,et al.  A role for cytoplasmic dynein and LIS1 in directed cell movement , 2003, The Journal of cell biology.

[17]  R. Ramos,et al.  RNAi reveals doublecortin is required for radial migration in rat neocortex , 2003, Nature Neuroscience.

[18]  B. Slepchenko,et al.  Centrosome positioning in interphase cells , 2003, The Journal of cell biology.

[19]  Christopher P Austin,et al.  DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation. , 2003, Human molecular genetics.

[20]  D. Ledbetter,et al.  14-3-3ε is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller–Dieker syndrome , 2003, Nature Genetics.

[21]  G. Eichele,et al.  Previously uncharacterized roles of platelet-activating factor acetylhydrolase 1b complex in mouse spermatogenesis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Taketo,et al.  Targeted Disruption of Intracellular Type I Platelet Activating Factor-acetylhydrolase Catalytic Subunits Causes Severe Impairment in Spermatogenesis* , 2003, The Journal of Biological Chemistry.

[23]  A. Wynshaw-Boris,et al.  Multiple Dose-Dependent Effects of Lis1 on Cerebral Cortical Development , 2003, The Journal of Neuroscience.

[24]  J. Cooper,et al.  The role of the lissencephaly protein Pac1 during nuclear migration in budding yeast , 2003, The Journal of cell biology.

[25]  J. Sibarita,et al.  Microtubule release from the centrosome in migrating cells , 2002, The Journal of cell biology.

[26]  N. Galjart,et al.  Cytoplasmic linker proteins promote microtubule rescue in vivo , 2002, The Journal of cell biology.

[27]  C. Hoogenraad,et al.  LIS1, CLIP-170's Key to the Dynein/Dynactin Pathway , 2002, Molecular and Cellular Biology.

[28]  R. Vallee,et al.  Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function , 2002, The Journal of cell biology.

[29]  S. Mcconnell,et al.  NudC Associates with Lis1 and the Dynein Motor at the Leading Pole of Neurons , 2001, The Journal of Neuroscience.

[30]  R. Vallee,et al.  Cdc42, dynein, and dynactin regulate MTOC reorientation independent of Rho-regulated microtubule stabilization , 2001, Current Biology.

[31]  A. Hall,et al.  Integrin-Mediated Activation of Cdc42 Controls Cell Polarity in Migrating Astrocytes through PKCζ , 2001, Cell.

[32]  Gongshe Han,et al.  The Aspergillus cytoplasmic dynein heavy chain and NUDF localize to microtubule ends and affect microtubule dynamics , 2001, Current Biology.

[33]  A. Wynshaw-Boris,et al.  A LIS1/NUDEL/Cytoplasmic Dynein Heavy Chain Complex in the Developing and Adult Nervous System , 2000, Neuron.

[34]  C. Walsh,et al.  LIS1 Regulates CNS Lamination by Interacting with mNudE, a Central Component of the Centrosome , 2000, Neuron.

[35]  Li-Huei Tsai,et al.  NUDEL Is a Novel Cdk5 Substrate that Associates with LIS1 and Cytoplasmic Dynein , 2000, Neuron.

[36]  L. Tsai,et al.  Regulation of cytoplasmic dynein behaviour and microtubule organization by mammalian Lis1 , 2000, Nature Cell Biology.

[37]  R. Vallee,et al.  A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function , 2000, Nature Cell Biology.

[38]  Y. Lei,et al.  The Drosophila Lissencephaly1 (DLis1) gene is required for nuclear migration. , 2000, Developmental biology.

[39]  Hiroyuki Arai,et al.  Direct association of LIS1, the lissencephaly gene product, with a mammalian homologue of a fungal nuclear distribution protein, rNUDE , 2000, FEBS letters.

[40]  N. Morris,et al.  The Lis1-Related Nudf Protein of Aspergillus nidulans Interacts with the Coiled-Coil Domain of the Nude/Ro11 Protein , 2000, The Journal of cell biology.

[41]  G. Eichele,et al.  Lissencephaly associated mutations suggest a requirement for the PAFAH1B heterotrimeric complex in brain development , 2000, Mechanisms of Development.

[42]  A. Wynshaw-Boris,et al.  Hippocampal Abnormalities and Enhanced Excitability in a Murine Model of Human Lissencephaly , 2000, The Journal of Neuroscience.

[43]  B. Suter,et al.  Drosophila Lissencephaly-1 functions with Bic-D and dynein in oocyte determination and nuclear positioning , 1999, Nature Cell Biology.

[44]  R. Steward,et al.  Lis1, the Drosophila homolog of a human lissencephaly disease gene, is required for germline cell division and oocyte differentiation. , 1999, Development.

[45]  C. Walsh,et al.  Doublecortin Is a Microtubule-Associated Protein and Is Expressed Widely by Migrating Neurons , 1999, Neuron.

[46]  D. Ledbetter,et al.  Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality , 1998, Nature Genetics.

[47]  G. Eichele,et al.  The lissencephaly gene product Lis1, a protein involved in neuronal migration, interacts with a nuclear movement protein, NudC , 1998, Current Biology.

[48]  D. Dujardin,et al.  Dynein and dynactin are localized to astral microtubules and at cortical sites in mitotic epithelial cells , 1998, Current Biology.

[49]  C. Echeverri,et al.  Cytoplasmic Dynein and Dynactin Are Required for the Transport of Microtubules into the Axon , 1998, The Journal of cell biology.

[50]  I. Scheffer,et al.  doublecortin , a Brain-Specific Gene Mutated in Human X-Linked Lissencephaly and Double Cortex Syndrome, Encodes a Putative Signaling Protein , 1998, Cell.

[51]  Y. Berwald‐Netter,et al.  A Novel CNS Gene Required for Neuronal Migration and Involved in X-Linked Subcortical Laminar Heterotopia and Lissencephaly Syndrome , 1998, Cell.

[52]  O. Reiner,et al.  Reduction of microtubule catastrophe events by LIS1, platelet‐activating factor acetylhydrolase subunit , 1997, The EMBO journal.

[53]  D. Ledbetter,et al.  Point mutations and an intragenic deletion in LIS1, the lissencephaly causative gene in isolated lissencephaly sequence and Miller-Dieker syndrome. , 1997, Human molecular genetics.

[54]  S. Osmani,et al.  NudF, a nuclear migration gene in Aspergillus nidulans, is similar to the human LIS-1 gene required for neuronal migration. , 1995, Molecular biology of the cell.

[55]  H. Arai,et al.  Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor , 1994, Nature.

[56]  I R Gibbons,et al.  Cytoplasmic dynein is required for normal nuclear segregation in yeast. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[57]  Y. Li,et al.  Disruption of mitotic spindle orientation in a yeast dynein mutant. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[58]  D. Ledbetter,et al.  Isolation of a Miller–Dicker lissencephaly gene containing G protein β-subunit-like repeats , 1993, Nature.

[59]  A. Barkovich,et al.  The spectrum of lissencephaly: Report of ten patients analyzed by magnetic resonance imaging , 1991, Annals of neurology.

[60]  R. Vallee,et al.  Isolated flagellar outer arm dynein translocates brain microtubules in vitro , 1987, Nature.

[61]  R. Vallee,et al.  Retrograde transport by the microtubule-associated protein MAP 1C , 1987, Nature.

[62]  M. Ross.  Brain malformations, epilepsy, and infantile spasms. , 2002, International review of neurobiology.

[63]  C. Truwit,et al.  Lissencephaly and other malformations of cortical development: 1995 update. , 1995, Neuropediatrics.

[64]  D. Ledbetter,et al.  Isolation of a Miller-Dieker lissencephaly gene containing G protein beta-subunit-like repeats. , 1993, Nature.