Article abstract
Nature Neuroscience 10, 819 - 827 (2007)
Published online: 24 June 2007 | doi:10.1038/nn1924
Numb and Numbl are required for maintenance of cadherin-based adhesion and polarity of neural progenitors
Mladen-Roko Ra
in1,
Valeswara-Rao Gazula1,
Joshua J Breunig1,
Kenneth Y Kwan1,
Matthew B Johnson1,
Susan Liu-Chen1,
Hua-Shun Li2,3,
Lily Yeh Jan2,
Yuh-Nung Jan2,
Pasko Rakic1
&
Nenad 
estan1
Abstract
The polarity and adhesion of radial glial cells (RGCs), which function as progenitors and migrational guides for neurons, are critical for morphogenesis of the cerebral cortex. These characteristics largely depend on cadherin-based adherens junctions, which anchor apical end-feet of adjacent RGCs to each other at the ventricular surface. Here, we show that mouse numb and numb-like are required for maintaining radial glial adherens junctions. Numb accumulates in the apical end-feet, where it localizes to adherens junction–associated vesicles and interacts with cadherins. Numb and Numbl inactivation in RGCs decreases proper basolateral insertion of cadherins and disrupts adherens junctions and polarity, leading to progenitor dispersion and disorganized cortical lamination. Conversely, overexpression of Numb prolongs RGC polarization, in a cadherin-dependent manner, beyond the normal neurogenic period. Thus, by regulating RGC adhesion and polarity, Numb and Numbl are required for the tissue architecture of neurogenic niches and the cerebral cortex.
- Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.
- Howard Hughes Medical Institute, Departments of Physiology and Biochemistry, University of California San Francisco, 1550 4th Street, San Francisco, California 94143, USA.
- Developmental Neurobiology Program, Institute of Molecular Medicine and Genetics, Medical College of Georgia, 1120 15th Street, Augusta, Georgia 30912, USA.
Correspondence to: Nenad estan1
e-mail: nenad.sestan@yale.edu
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