Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates.
The development of the vertebrate brain requires an exquisite balance between proliferation and differentiation of neural progenitors. Notch signaling plays a pivotal role in regulating this balance, yet the interaction between signaling and receiving cells remains poorly understood. We have found that numerous nascent neurons and/or intermediate neurogenic progenitors expressing the ligand of Notch retain apical endfeet transiently at the ventricular lumen that form adherens junctions (AJs) with the endfeet of progenitors. Forced detachment of the apical endfeet of those differentiating cells by disrupting AJs resulted in precocious neurogenesis that was preceded by the downregulation of Notch signaling. Both Notch1 and its ligand Dll1 are distributed around AJs in the apical endfeet, and these proteins physically interact with ZO-1, a constituent of the AJ. Furthermore, live imaging of a fluorescently tagged Notch1 demonstrated its trafficking from the apical endfoot to the nucleus upon cleavage. Our results identified the apical endfoot as the central site of active Notch signaling to securely prohibit inappropriate differentiation of neural progenitors.
Department of Brain Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
Jun
J
Hatakeyama
Yoshio
Y
Wakamatsu
Akira
A
Nagafuchi
Ryoichiro
R
Kageyama
Ryuichi
R
Shigemoto
Kenji
K
Shimamura
D022005:Adherens Junctions / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000648:ultrastructure; D015820:Cadherins / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002448:Cell Adhesion; D002645:Chickens; D021621:Imaging, Three-Dimensional; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D014714:Vertebrates / Q000378:metabolism*
D015820:Cadherins; D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051880:Receptors, Notch
Adherens junction; Apical endfoot; Cadherin; Chick; Mouse; Neural stem/progenitor cell; Neurogenesis; Notch signaling