Open AccessIsozyme-Specific Role of SAD-A in Neuronal Migration During Development of Cerebral Cortex
Author(s) -
Kazuyoshi Nakanishi,
Hiroyuki Niida,
Hidenori Tabata,
Tsuyoshi Ito,
Yuki Hori,
Madoka Hattori,
Yoshikazu Johmura,
Chizumi Yamada,
Takashi Ueda,
Kosei Takeuchi,
Kenichiro Yamada,
Kohichi Nagata,
Nobuaki Wakamatsu,
Masashi Kishi,
Y. Albert Pan,
Shinya Ugawa,
Shoichi Shimada,
Joshua R. Sanes,
Youichirou Higashi,
Makoto Nakanishi
Publication year - 2018
Publication title -
cerebral cortex
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.694
H-Index - 250
eISSN - 1460-2199
pISSN - 1047-3211
DOI - 10.1093/cercor/bhy253
Subject(s) - hippocampal formation , cerebral cortex , biology , neurite , neuroscience , cortical dysplasia , neurogenesis , cortex (anatomy) , cortical neurons , mutant , microbiology and biotechnology , epilepsy , gene , genetics , in vitro
SAD kinases regulate presynaptic vesicle clustering and neuronal polarization. A previous report demonstrated that Sada-/- and Sadb-/- double-mutant mice showed perinatal lethality with a severe defect in axon/dendrite differentiation, but their single mutants did not. These results indicated that they were functionally redundant. Surprisingly, we show that on a C57BL/6N background, SAD-A is essential for cortical development whereas SAD-B is dispensable. Sada-/- mice died within a few days after birth. Their cortical lamination pattern was disorganized and radial migration of cortical neurons was perturbed. Birth date analyses with BrdU and in utero electroporation using pCAG-EGFP vector showed a delayed migration of cortical neurons to the pial surface in Sada-/- mice. Time-lapse imaging of these mice confirmed slow migration velocity in the cortical plate. While the neurites of hippocampal neurons in Sada-/- mice could ultimately differentiate in culture to form axons and dendrites, the average length of their axons was shorter than that of the wild type. Thus, analysis on a different genetic background than that used initially revealed a nonredundant role for SAD-A in neuronal migration and differentiation.