Synergistic Effects of MAP2 and MAP1B Knockout in Neuronal Migration, Dendritic Outgrowth, and Microtubule Organization

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2001 Oct 3

PMID 11581286

Citations 121

Authors

J Teng

Y Takei

A Harada

T Nakata

J Chen

N Hirokawa

Affiliations

Soon will be listed here.

Abstract

MAP1B and MAP2 are major members of neuronal microtubule-associated proteins (MAPs). To gain insights into the function of MAP2 in vivo, we generated MAP2-deficient (map2(-/-)) mice. They developed without any apparent abnormalities, which indicates that MAP2 is dispensable in mouse survival. Because previous reports suggest a functional redundancy among MAPs, we next generated mice lacking both MAP2 and MAP1B to test their possible synergistic functions in vivo. Map2(-/-)map1b(-/-) mice died in their perinatal period. They showed not only fiber tract malformations but also disrupted cortical patterning caused by retarded neuronal migration. In spite of this, their cortical layer maintained an "inside-out" pattern. Detailed observation of primary cultures of hippocampal neurons from map2(-/-)map1b(-/-) mice revealed inhibited microtubule bundling and neurite elongation. In these neurons, synergistic effects caused by the loss of MAP2 and MAP1B were more apparent in dendrites than in axons. The spacing of microtubules was reduced significantly in map2(-/-)map1b(-/-) mice in vitro and in vivo. These results suggest that MAP2 and MAP1B have overlapping functions in neuronal migration and neurite outgrowth by organizing microtubules in developing neurons both for axonal and dendritic morphogenesis but more dominantly for dendritic morphogenesis.

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References

Sanchez C, Diaz-Nido J, Avila J . Phosphorylation of microtubule-associated protein 2 (MAP2) and its relevance for the regulation of the neuronal cytoskeleton function. Prog Neurobiol. 2000; 61(2):133-68. DOI: 10.1016/s0301-0082(99)00046-5. View

Edelmann W, Zervas M, Costello P, Roback L, Fischer I, Hammarback J . Neuronal abnormalities in microtubule-associated protein 1B mutant mice. Proc Natl Acad Sci U S A. 1996; 93(3):1270-5. PMC: 40069. DOI: 10.1073/pnas.93.3.1270. View

Gonzalez-Billault C, Demandt E, Wandosell F, Torres M, Bonaldo P, Stoykova A . Perinatal lethality of microtubule-associated protein 1B-deficient mice expressing alternative isoforms of the protein at low levels. Mol Cell Neurosci. 2000; 16(4):408-21. DOI: 10.1006/mcne.2000.0880. View

Meixner A, Haverkamp S, Wassle H, Fuhrer S, Thalhammer J, Kropf N . MAP1B is required for axon guidance and Is involved in the development of the central and peripheral nervous system. J Cell Biol. 2000; 151(6):1169-78. PMC: 2190583. DOI: 10.1083/jcb.151.6.1169. View

Garcia M, Cleveland D . Going new places using an old MAP: tau, microtubules and human neurodegenerative disease. Curr Opin Cell Biol. 2001; 13(1):41-8. DOI: 10.1016/s0955-0674(00)00172-1. View

Rakic P, Knyihar-Csillik E, Csillik B . Polarity of microtubule assemblies during neuronal cell migration. Proc Natl Acad Sci U S A. 1996; 93(17):9218-22. PMC: 38622. DOI: 10.1073/pnas.93.17.9218. View

Ohshima T, Ward J, Huh C, Longenecker G, Veeranna , Pant H . Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc Natl Acad Sci U S A. 1996; 93(20):11173-8. PMC: 38303. DOI: 10.1073/pnas.93.20.11173. View

Chae T, Kwon Y, Bronson R, Dikkes P, Li E, Tsai L . Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron. 1997; 18(1):29-42. DOI: 10.1016/s0896-6273(01)80044-1. View

Cunningham C, Leclerc N, Flanagan L, Lu M, Janmey P, Kosik K . Microtubule-associated protein 2c reorganizes both microtubules and microfilaments into distinct cytological structures in an actin-binding protein-280-deficient melanoma cell line. J Cell Biol. 1997; 136(4):845-57. PMC: 2132495. DOI: 10.1083/jcb.136.4.845. View

10.

Takei Y, Kondo S, Harada A, Inomata S, Noda T, Hirokawa N . Delayed development of nervous system in mice homozygous for disrupted microtubule-associated protein 1B (MAP1B) gene. J Cell Biol. 1997; 137(7):1615-26. PMC: 2137829. DOI: 10.1083/jcb.137.7.1615. View

11.

Sheldon M, Rice D, DArcangelo G, Yoneshima H, Nakajima K, Mikoshiba K . Scrambler and yotari disrupt the disabled gene and produce a reeler-like phenotype in mice. Nature. 1997; 389(6652):730-3. DOI: 10.1038/39601. View

12.

Sapir T, Elbaum M, Reiner O . Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit. EMBO J. 1998; 16(23):6977-84. PMC: 1170301. DOI: 10.1093/emboj/16.23.6977. View

13.

Paglini G, Pigino G, Kunda P, Morfini G, Maccioni R, Quiroga S . Evidence for the participation of the neuron-specific CDK5 activator P35 during laminin-enhanced axonal growth. J Neurosci. 1998; 18(23):9858-69. PMC: 6793278. View

14.

Trommsdorff M, Gotthardt M, Hiesberger T, Shelton J, STOCKINGER W, Nimpf J . Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2. Cell. 1999; 97(6):689-701. DOI: 10.1016/s0092-8674(00)80782-5. View

15.

Francis F, Koulakoff A, Boucher D, Chafey P, Schaar B, Vinet M . Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron. 1999; 23(2):247-56. DOI: 10.1016/s0896-6273(00)80777-1. View

16.

Gleeson J, Lin P, Flanagan L, Walsh C . Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron. 1999; 23(2):257-71. DOI: 10.1016/s0896-6273(00)80778-3. View

17.

Yoneshima H, Nagata E, Matsumoto M, Yamada M, Nakajima K, Miyata T . A novel neurological mutant mouse, yotari, which exhibits reeler-like phenotype but expresses CR-50 antigen/reelin. Neurosci Res. 1998; 29(3):217-23. DOI: 10.1016/s0168-0102(97)00088-6. View

18.

Nakata T, Terada S, Hirokawa N . Visualization of the dynamics of synaptic vesicle and plasma membrane proteins in living axons. J Cell Biol. 1998; 140(3):659-74. PMC: 2140163. DOI: 10.1083/jcb.140.3.659. View

19.

Gleeson J, Allen K, Fox J, Lamperti E, Berkovic S, Scheffer I . Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell. 1998; 92(1):63-72. DOI: 10.1016/s0092-8674(00)80899-5. View

20.

Portes V, Francis F, Pinard J, Desguerre I, Moutard M, Snoeck I . doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH). Hum Mol Genet. 1998; 7(7):1063-70. DOI: 10.1093/hmg/7.7.1063. View