Regulation of neurogenesis by interkinetic nuclear migration through an apical-basal notch gradient.
The different cell types in the central nervous system develop from a common pool of progenitor cells. The nuclei of progenitors move between the apical and basal surfaces of the neuroepithelium in phase with their cell cycle, a process termed interkinetic nuclear migration (INM). In the retina of zebrafish mikre oko (mok) mutants, in which the motor protein Dynactin-1 is disrupted, interkinetic nuclei migrate more rapidly and deeply to the basal side and more slowly to the apical side. We found that Notch signaling is predominantly activated on the apical side in both mutants and wild-type. Mutant progenitors are, thus, less exposed to Notch and exit the cell cycle prematurely. This leads to an overproduction of early-born retinal ganglion cells (RGCs) at the expense of later-born interneurons and glia. Our data indicate that the function of INM is to balance the exposure of progenitor nuclei to neurogenic versus proliferative signals.
Del Bene
Filippo
F
Department of Physiology, Programs in Neuroscience, Genetics, and Developmental Biology, University of California San Francisco, San Francisco, CA 94158-2722, USA.
Wehman
Ann M
AM
Link
Brian A
BA
Baier
Herwig
H
D000818:Animals; D019521:Body Patterning; D002453:Cell Cycle; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D000072159:Dynactin Complex; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009154:Mutation; D046569:Neuroepithelial Cells / Q000166:cytology* / Q000378:metabolism; D038081:Organogenesis; D051880:Receptors, Notch / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D051880:Receptors, Notch; D029961:Zebrafish Proteins