Instructive role of aPKCζ subcellular localization in the assembly of adherens junctions in neural progenitors

*Molecular and Cell Biology Laboratory and
^‡Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037

Edited by Fred H. Gage, Salk Institute for Biological Studies, San Diego, CA, and approved November 12, 2007 (received for review June 18, 2007)

Abstract

In the neurogenic phase of CNS development, the proliferating progenitors are found medially within the neuroepithelium. The adherens junctions on the apical membrane of proliferating neural progenitors allow for cell–cell adhesion and medial stratification. In contrast, differentiating neuronal precursors delaminate and migrate laterally, establishing the laminar layers. Apical adherens junctions also establish the apical–basal polarity in neural progenitors, which in turn is postulated to lead to asymmetric inheritance of cell fate determinants during neurogenic divisions. The signaling pathways and cellular mechanisms that regulate the assembly and asymmetric localization of adherens junctions in neural progenitors remain elusive. Here we show that atypical PKCζ/λ (aPKCζ/λ) localizes at the apical membrane of proliferating neural stem cells, but not postmitotic neuronal precursors, in the developing chicken neural tube. This precise subcellular compartmentalization of the kinase activity provides an instructive signal for apical assembly of adherens junctions in a PI3K, Rac/Cdc42 signaling-dependent pathway. Apical aPKCζ coordinates neural stem cell proliferation and the overall stratification of cell types within the neural tube.

Footnotes

^‖To whom correspondence may be addressed. E-mail: pfaff{at}salk.edu or hunter{at}salk.edu
Author contributions: S.G., T.M., and J.P.T. designed research; S.G., T.M., J.P.T., and S.E.A. performed research; N.C. contributed new reagents/analytic tools; S.G., S.L.P., and T.H. analyzed data; and S.G. wrote the paper.
↵ ^†Present address: Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ 85012.
↵ ^§Present address: European Neuroscience Institute, 37077 Göttingen, Germany.
↵ ^¶Present address: University of Washington Medical Center, Seattle, WA 98195.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0705713105/DC1.