TAG-1-assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding.
Neural progenitors exhibit cell cycle-dependent interkinetic nuclear migration (INM) along the apicobasal axis. Despite recent advances in understanding its underlying molecular mechanisms, the processes to which INM contributes mechanically and the regulation of INM by the apicobasally elongated morphology of progenitors remain unclear. We found that knockdown of the cell-surface molecule TAG-1 resulted in retraction of neocortical progenitors' basal processes. Highly shortened stem-like progenitors failed to undergo basalward INM and became overcrowded in the periventricular (subapical) space. Surprisingly, the overcrowded progenitors left the apical surface and migrated into basal neuronal territories. These observations, together with the results of in toto imaging and physical tests, suggest that progenitors may sense and respond to excessive mechanical stress. Although, unexpectedly, the heterotopic progenitors remained stem-like and continued to sequentially produce neurons until the late embryonic period, histogenesis was severely disrupted. Thus, INM is essential for preventing overcrowding of nuclei and their somata, thereby ensuring normal brain histogenesis.
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Mayumi
M
Okamoto
Takashi
T
Namba
Tomoyasu
T
Shinoda
Takefumi
T
Kondo
Tadashi
T
Watanabe
Yasuhiro
Y
Inoue
Kosei
K
Takeuchi
Yukiko
Y
Enomoto
Kumiko
K
Ota
Kanako
K
Oda
Yoshino
Y
Wada
Ken
K
Sagou
Kanako
K
Saito
Akira
A
Sakakibara
Ayano
A
Kawaguchi
Kazunori
K
Nakajima
Taiji
T
Adachi
Toshihiko
T
Fujimori
Masahiro
M
Ueda
Shigeo
S
Hayashi
Kozo
K
Kaibuchi
Takaki
T
Miyata
D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000166:cytology; D003198:Computer Simulation; D058969:Contactin 2 / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian; D004848:Epithelium / Q000196:embryology / Q000502:physiology; D006657:Histones / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology / Q000648:ultrastructure*; D009924:Organ Culture Techniques; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000378:metabolism; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism
C548675:Cntn2 protein, mouse; D058969:Contactin 2; D006657:Histones; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse