Defects in Axonal Elongation and Neuronal Migration in Mice with Disrupted tau and map1b Genes

Takei, Yosuke; Teng, Junlin; Harada, Akihiro; Hirokawa, Nobutaka

doi:info:doi/10.1083/jcb.150.5.989

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タイトル	Defects in Axonal Elongation and Neuronal Migration in Mice with Disrupted tau and map1b Genes
著者	Takei, Yosuke Takei, Yosuke
	Teng, Junlin Teng, Junlin
	Harada, Akihiro Harada, Akihiro
	Hirokawa, Nobutaka Hirokawa, Nobutaka
キーワード等	tau
	MAP1B
	axon
	growth cone
	neuronal migration
抄録	Tau and MAP1B are the main members of neuronal microtubule-associated proteins (MAPs), the functions of which have remained obscure because of a putative functional redundancy (Harada, A., K. Oguchi, S. Okabe, J. Kuno, S. Terada, T. Ohshima, R. SatoYoshitake, Y. Takei, T. Noda, and N. Hirokawa. 1994. Nature. 369:488–491; Takei, Y., S. Kondo, A. Harada, S. Inomata, T. Noda, and N. Hirokawa. 1997. J. Cell Biol. 137:1615–1626). To unmask the role of these proteins, we generated double-knockout mice with disrupted tau and map1b genes and compared their phenotypes with those of single-knockout mice. In the analysis of mice with a genetic background of predominantly C57Bl/6J, a hypoplastic commissural axon tract and disorganized neuronal layering were observed in the brains of the tau +/+map1b-/-mice. These phenotypes are markedly more severe in tau -/-map1b-/-double mutants, indicating that tau and MAP1B act in a synergistic fashion. Primary cultures of hippocampal neurons from tau -/-map1b-/-mice showed inhibited axonal elongation. In these cells, a generation of new axons via bundling of microtubules at the neck of the growth cones appeared to be disturbed. Cultured cerebellar neurons from tau -/-map1b-/-mice showed delayed neuronal migration concomitant with suppressed neurite elongation. These findings indicate the cooperative functions of tau and MAP1B in vivo in axonal elongation and neuronal migration as regulators of microtubule oganization.
公開者	The Rockefeller University Press
掲載誌名	Journal of Cell Biology
巻	150
号	5
開始ページ	989
終了ページ	1000
刊行年月	2000-09-04
ISSN	00219525
NCID	AA00694812
DOI	info:doi/10.1083/jcb.150.5.989
URL	http://hdl.handle.net/11094/23081
言語	英語
カテゴリ	学術雑誌論文 Journal Article

著者版フラグ	publisher
NII資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
dcmi資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Cell Biology.150(5) P.989-P.1000
DC.title	Defects in Axonal Elongation and Neuronal Migration in Mice with Disrupted tau and map1b Genes
DC.creator	Takei, Yosuke
	Teng, Junlin
	Harada, Akihiro
	Hirokawa, Nobutaka
DC.publisher	The Rockefeller University Press
DC.language" scheme="DCTERMS.RFC1766	英語
DCTERMS.issued" scheme="DCTERMS.W3CDTF	2000-09-04
DC.identifier	info:doi/10.1083/jcb.150.5.989
DC.identifier" scheme="DCTERMS.URI	http://hdl.handle.net/11094/23081
DC.subject	tau
	MAP1B
	axon
	growth cone
	neuronal migration
DCTERMS.abstract	Tau and MAP1B are the main members of neuronal microtubule-associated proteins (MAPs), the functions of which have remained obscure because of a putative functional redundancy (Harada, A., K. Oguchi, S. Okabe, J. Kuno, S. Terada, T. Ohshima, R. SatoYoshitake, Y. Takei, T. Noda, and N. Hirokawa. 1994. Nature. 369:488–491; Takei, Y., S. Kondo, A. Harada, S. Inomata, T. Noda, and N. Hirokawa. 1997. J. Cell Biol. 137:1615–1626). To unmask the role of these proteins, we generated double-knockout mice with disrupted tau and map1b genes and compared their phenotypes with those of single-knockout mice. In the analysis of mice with a genetic background of predominantly C57Bl/6J, a hypoplastic commissural axon tract and disorganized neuronal layering were observed in the brains of the tau +/+map1b-/-mice. These phenotypes are markedly more severe in tau -/-map1b-/-double mutants, indicating that tau and MAP1B act in a synergistic fashion. Primary cultures of hippocampal neurons from tau -/-map1b-/-mice showed inhibited axonal elongation. In these cells, a generation of new axons via bundling of microtubules at the neck of the growth cones appeared to be disturbed. Cultured cerebellar neurons from tau -/-map1b-/-mice showed delayed neuronal migration concomitant with suppressed neurite elongation. These findings indicate the cooperative functions of tau and MAP1B in vivo in axonal elongation and neuronal migration as regulators of microtubule oganization.
citation_title	Defects in Axonal Elongation and Neuronal Migration in Mice with Disrupted tau and map1b Genes
citation_author	Takei, Yosuke
	Teng, Junlin
	Harada, Akihiro
	Hirokawa, Nobutaka
citation_publisher	The Rockefeller University Press
citation_language	英語
citation_date	2000-09-04
citation_journal_title	Journal of Cell Biology
citation_volume	150
citation_issue	5
citation_firstpage	989
citation_lastpage	1000
citation_issn	00219525
citation_doi	info:doi/10.1083/jcb.150.5.989
citation_public_url	http://hdl.handle.net/11094/23081
citation_keywords	tau
	MAP1B
	axon
	growth cone
	neuronal migration

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