Numb and Numbl are required for maintenance of cadherin-based adhesion and polarity of neural progenitors.
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.
Rasin
Mladen-Roko
MR
Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.
Gazula
Valeswara-Rao
VR
Breunig
Joshua J
JJ
Kwan
Kenneth Y
KY
Johnson
Matthew B
MB
Liu-Chen
Susan
S
Li
Hua-Shun
HS
Jan
Lily Yeh
LY
Jan
Yuh-Nung
YN
Rakic
Pasko
P
Sestan
Nenad
N
D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000502:physiology; D018274:Electroporation; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*
D015820:Cadherins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; C106292:Numbl protein, mouse; D012313:RNA