Synergistic effects of MAP2 and MAP1B knockout in neuronal migration, dendritic outgrowth, and microtubule organization

Citation
Jl. Teng et al., Synergistic effects of MAP2 and MAP1B knockout in neuronal migration, dendritic outgrowth, and microtubule organization, J CELL BIOL, 155(1), 2001, pp. 65-76
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
155
Issue
1
Year of publication
2001
Pages
65 - 76
Database
ISI
SICI code
0021-9525(20011001)155:1<65:SEOMAM>2.0.ZU;2-F
Abstract
MAP1B and MAP2 are major members of neuronal microtubule-associated protein s (MAPs). To gain insights into the function of MAP2 in vivo, we generated MAP2-deficient (map2(-/-)) mice. They developed without any apparent abnorm alities, which indicates that MAP2 is dispensable in mouse survival. Becaus e previous reports suggest a functional redundancy among MAPs, we next gene rated mice lacking both MAP2 and MAP1 B 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 revea led inhibited microtubule bundling and neurite elongation. In these neurons , synergistic effects caused by the loss of MAP2 and MAP1B were more appare nt in dendrites than in axons. The spacing of microtubules was reduced sign ificantly in map2(-/-)map1b(-/-) mice in vitro and in vivo. These results s uggest that MAP2 and MAP1 B have overlapping functions in neuronal migratio n and neurite outgrowth by organizing microtubules in developing neurons bo th for axonal and dendritic morphogenesis but more dominantly for dendritic morphogenesis.