Inactivation of aPKClambda results in the loss of adherens junctions in neuroepithelial cells without affecting neurogenesis in mouse neocortex.
In developing mammalian telencephalon, the loss of adherens junctions and cell cycle exit represent crucial steps in the differentiation of neuroepithelial cells into neurons, but the relationship between these cellular events remains obscure. Atypical protein kinase C (aPKC) is known to contribute to junction formation in epithelial cells and to cell fate determination for Drosophila neuroblasts. To elucidate the functions of aPKClambda, one out of two aPKC members, in mouse neocortical neurogenesis, a Nestin-Cre mediated conditional gene targeting system was employed. In conditional aPKClambda knockout mice, neuroepithelial cells of the neocortical region lost aPKClambda protein at embryonic day 15 and demonstrated a loss of adherens junctions, retraction of apical processes and impaired interkinetic nuclear migration that resulted in disordered neuroepithelial tissue architecture. These results are evidence that aPKClambda is indispensable for the maintenance of adherens junctions and may function in the regulation of adherens junction integrity upon differentiation of neuroepithelial cells into neurons. In spite of the loss of adherens junctions in the neuroepithelium of conditional aPKClambda knockout mice, neurons were produced at a normal rate. Therefore, we concluded that, at least in the later stages of neurogenesis, regulation of cell cycle exit is independent of adherens junctions.
Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
Fumiyasu
F
Imai
Syu-ichi
S
Hirai
Kazunori
K
Akimoto
Hiromichi
H
Koyama
Takaki
T
Miyata
Masaharu
M
Ogawa
Shigeru
S
Noguchi
Toshikuni
T
Sasaoka
Tetsuo
T
Noda
Shigeo
S
Ohno
D022005:Adherens Junctions / Q000648:ultrastructure; D000818:Animals; D002478:Cells, Cultured; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D019579:Neocortex / Q000166:cytology* / Q000196:embryology / Q000502:physiology* / Q000648:ultrastructure; D046569:Neuroepithelial Cells / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D013687:Telencephalon / Q000166:cytology
D007527:Isoenzymes; C115015:PKC-3 protein; D011493:Protein Kinase C