Rac1 in cortical projection neurons is selectively required for midline crossing of commissural axonal formation.
Rac1 is a member of Rho family GTPases and regulates multiple cellular functions through actin cytoskeleton reorganization. During cerebral corticogenesis, Rac1 has been assumed to be involved in neuronal migration, neurite formation, polarization and axonal guidance. Here we show the specific role of Rac1, regulating midline crossing of commissural axons during cortical development by using cortex-restricted Rac1-knockout mice. In the knockout mice, Rac1 was eliminated from the beginning of corticogenesis exclusively in the dorsal telencephalon where progenitors of cortical projection neurons are located. Cortical lamination was distorted only mildly in the knockout mice, being preserved with six layers of neurons. However, cortex-restricted Rac1 deletion exhibited striking agenesis of commissural axons including the corpus callosum and anterior commissure without affecting other corticofugal axons including corticospinal and corticothalamic projections. Of note, the commissural axons of the knockout mice were potent in extending their process, but failed to cross the midline. Therefore, these findings indicate that Rac1 specifically controls the midline crossing of the commissural fibers, but not axonal formation of corticospinal or corticothalamic fibers during cortical development.
Kassai
Hidetoshi
H
Division of Molecular Genetics, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Terashima
Toshio
T
Fukaya
Masahiro
M
Nakao
Kazuki
K
Sakahara
Mizuho
M
Watanabe
Masahiko
M
Aiba
Atsu
A
D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D002540:Cerebral Cortex / Q000002:abnormalities / Q000254:growth & development / Q000473:pathology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D009479:Neuropeptides / Q000172:deficiency / Q000378:metabolism*; D011712:Pyramidal Tracts / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D013687:Telencephalon / Q000378:metabolism; D013788:Thalamus / Q000502:physiology; D014018:Tissue Distribution; D020744:rac GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein
D009479:Neuropeptides; C484602:Rac1 protein, mouse; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein