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PMID: 19640478 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mammalian Par3 regulates progenitor cell asymmetric division via notch signaling in the developing neocortex.

Neuron ·Vol. 63 ·No. 2 ·2009-07-30 ·Pages 189-202

Bultje RS, Castaneda-Castellanos DR, Jan LY, Jan YN, Kriegstein AR, Shi SH

Abstract

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Animals Cell Adhesion Molecules/genetics,metabolism Cell Cycle Proteins Cell Division/genetics,physiology Cell Polarity/genetics,physiology Electroporation Embryo, Mammalian/cytology Female Gene Expression Regulation, Developmental Immunohistochemistry Mice Microscopy, Confocal Neocortex/embryology,growth & development Neuroglia/metabolism,physiology Plasmids Pregnancy Receptors, Notch/metabolism,physiology Signal Transduction/genetics,physiology Stem Cells/metabolism,physiology
Chemicals
Adaptor Proteins, Signal Transducing Cell Adhesion Molecules Cell Cycle Proteins Pard3 protein, mouse Receptors, Notch
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bultje Ronald S
Developmental Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Castaneda-Castellanos David R
Jan Lily Yeh
Jan Yuh-Nung
Kriegstein Arnold R
Shi Song-Hai
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2009.07.004
Published
2009-07-30
Pages
189-202
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC2736606
Subset
IM
Grants
NIDA NIH HHS · R01 DA024681 · United States
NIDA NIH HHS · R01 DA024681-01A1 · United States
NIMH NIH HHS · R21 MH083624-01 · United States
NIMH NIH HHS · R21 MH083624-02 · United States
NIDA NIH HHS · R01 DA024681-02 · United States
NIMH NIH HHS · R21 MH083624 · United States
External Links
PubMed source DOI: 10.1016/j.neuron.2009.07.004 PMC Full Text View journal details
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