Cortical neural precursors inhibit their own differentiation via N-cadherin maintenance of beta-catenin signaling.
Little is known about the architecture of cellular microenvironments that support stem and precursor cells during tissue development. Although adult stem cell niches are organized by specialized supporting cells, in the developing cerebral cortex, neural stem/precursor cells reside in a neurogenic niche lacking distinct supporting cells. Here, we find that neural precursors themselves comprise the niche and regulate their own development. Precursor-precursor contact regulates beta-catenin signaling and cell fate. In vivo knockdown of N-cadherin reduces beta-catenin signaling, migration from the niche, and neuronal differentiation in vivo. N-cadherin engagement activates beta-catenin signaling via Akt, suggesting a mechanism through which cells in tissues can regulate their development. These results suggest that neural precursor cell interactions can generate a self-supportive niche to regulate their own number.
Zhang
Jianing
J
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Woodhead
Gregory J
GJ
Swaminathan
Sruthi K
SK
Noles
Stephanie R
SR
McQuinn
Erin R
ER
Pisarek
Anna J
AJ
Stocker
Adam M
AM
Mutch
Christopher A
CA
Funatsu
Nobuo
N
Chenn
Anjen
A
D000818:Animals; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D018274:Electroporation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
C495267:CTNNB1 protein, mouse; D015820:Cadherins; C489083:Cdh2 protein, mouse; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D051057:Proto-Oncogene Proteins c-akt