Mammalian Par3 regulates progenitor cell asymmetric division via notch signaling in the developing neocortex.
Asymmetric cell division of radial glial progenitors produces neurons while allowing self-renewal; however, little is known about the mechanism that generates asymmetry in daughter cell fate specification. Here, we found that mammalian partition defective protein 3 (mPar3), a key cell polarity determinant, exhibits dynamic distribution in radial glial progenitors. While it is enriched at the lateral membrane domain in the ventricular endfeet during interphase, mPar3 becomes dispersed and shows asymmetric localization as cell cycle progresses. Either removal or ectopic expression of mPar3 prevents radial glial progenitors from dividing asymmetrically yet generates different outcomes in daughter cell fate specification. Furthermore, the expression level of mPar3 affects Notch signaling, and manipulations of Notch signaling or Numb expression suppress mPar3 regulation of radial glial cell division and daughter cell fate specification. These results reveal a critical molecular pathway underlying asymmetric cell division of radial glial progenitors in the mammalian neocortex.
Bultje
Ronald S
RS
Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Castaneda-Castellanos
David R
DR
Jan
Lily Yeh
LY
Jan
Yuh-Nung
YN
Kriegstein
Arnold R
AR
Shi
Song-Hai
SH
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D018274:Electroporation; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D019579:Neocortex / Q000196:embryology / Q000254:growth & development*; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology*; D010957:Plasmids; D011247:Pregnancy; D051880:Receptors, Notch / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; C115084:Pard3 protein, mouse; D051880:Receptors, Notch