ERK1 and ERK2 are required for radial glial maintenance and cortical lamination

被引:28
作者
Imamura, Osamu [1 ]
Pages, Gilles [2 ]
Pouyssegur, Jacques [2 ]
Endo, Shogo [3 ]
Takishima, Kunio [1 ]
机构
[1] Natl Def Med Coll, Dept Biochem, Tokorozawa, Saitama 3598513, Japan
[2] Univ Nice Sophia Antipolis, Inst Signaling Dev Biol & Canc Res, CNRS, UMR 6543,Ctr A Lacassagne, F-06189 Nice, France
[3] Okinawa Inst Sci & Technol, Initial Res Project, Unit Mol Neurobiol Learning & Memory, Uruma 9042234, Japan
关键词
DEVELOPING CEREBRAL-CORTEX; ACTIVATED PROTEIN-KINASE; SIGNAL-REGULATED KINASE; CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELLS; NEURONAL MIGRATION; GANGLIONIC EMINENCE; BRAIN-DEVELOPMENT; SONIC HEDGEHOG; PRECURSORS;
D O I
10.1111/j.1365-2443.2010.01444.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
ERK1/2 is involved in a variety of cellular processes during development, but the functions of these isoforms in brain development remain to be determined. Here, we generated double knockout (DKO) mice to study the individual and combined roles of ERK1 and ERK2 during cortical development. Mice deficient in Erk2, and more dramatically in the DKOs, displayed proliferation defects in late radial glial progenitors within the ventricular zone, and a severe disruption of lamination in the cerebral cortex. Immunohistochemical analyses revealed that late-generated cortical neurons were misplaced and failed to migrate the upper cortical layers in DKO mice. Moreover, these mice displayed fewer radial glial fibers, which provide architectural guides for radially migrating neurons. These results suggest that extracellular signal-regulated kinase signaling is essential for the expansion of the radial glial population and for the maintenance of radial glial scaffolding. Tangential migration of interneurons and oligodendrocytes from the ganglionic eminences (GE) to the dorsal cortex was more severely impaired in DKO mice than in mice deficient for Erk2 alone, because of reduced progenitor proliferation in the GE of the ventral telencephalon. These data demonstrate functional overlaps between ERK1 and ERK2 and indicate that extracellular signal-regulated kinase signaling plays a crucial role in cortical development.
引用
收藏
页码:1072 / 1088
页数:17
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