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Development 129, 3479-3492 (2002)
© 2002 The Company of Biologists Limited

Absence of Cajal-Retzius cells and subplate neurons associated with defects of tangential cell migration from ganglionic eminence in Emx1/2 double mutant cerebral cortex

Koji Shinozaki1,*, Toshihiko Miyagi1,*, Michio Yoshida1, Takaki Miyata3, Masaharu Ogawa3, Shinichi Aizawa1,2,{dagger} and Yoko Suda1,2

1 Department of Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan
2 Vertebrate Body Plan Group, RIKEN Center for Developmental Biology, 2-2-3 Minatojima Minami, Chuou-ku, Kobe 650-0047, Japan
3 Laboratory for Cell Culture Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
* The first two authors contributed equally to this work

{dagger}Author for correspondence at address 2 (e-mail: saizawa{at}cdb.riken.go.jp)

Accepted 18 April 2002

Emx1 and Emx2, mouse orthologs of the Drosophila head gap gene, ems, are expressed during corticogenesis. Emx2 null mutants exhibit mild defects in cortical lamination. Segregation of differentiating neurons from proliferative cells is normal for the most part, however, reelin-positive Cajal-Retzius cells are lost by the late embryonic period. Additionally, late-born cortical plate neurons display abnormal position. These types of lamination defects are subtle in the Emx1 mutant cortex. In the present study we show that Emx1 and Emx2 double mutant neocortex is much more severely affected. Thickness of the cerebral wall was diminished with the decrease in cell number. Bromodeoxyuridine uptake in the germinal zone was nearly normal; moreover, no apparent increase in cell death or tetraploid cell number was observed. However, tangential migration of cells from the ganglionic eminence into the neocortex was greatly inhibited. The wild-type ganglionic eminence cells transplanted into Emx1/2-double mutant telencephalon did not move to the cortex. MAP2-positive neuronal bodies and RC2-positive radial glial cells emerged normally, but the laminar structure subsequently formed was completely abnormal. Furthermore, both corticofugal and corticopetal fibers were predominantly absent in the cortex. Most importantly, neither Cajal-Retzius cells nor subplate neurons were found throughout E11.5-E18.5. Thus, this investigation suggests that laminar organization in the cortex or the production of Cajal-Retzius cells and subplate neurons is interrelated to the tangential movement of cells from the ganglionic eminence under the control of Emx1 and Emx2.

Key words: Neocortex, Cortical lamination, Radial cell migration, Tangential cell migration, Emx1, Emx2, Cajal-Retzius cells, Subplate neurons, Pioneer neurons, Interneurons, Ganglionic eminence, Mouse







© The Company of Biologists Ltd 2002