APLP2 regulates neuronal stem cell differentiation during cortical development.
Expression of amyloid precursor protein (APP) and its two paralogues, APLP1 and APLP2 during brain development coincides with key cellular events such as neuronal differentiation and migration. However, genetic knockout and shRNA studies have led to contradictory conclusions about their role during embryonic brain development. To address this issue, we analysed in depth the role of APLP2 during neurogenesis by silencing APLP2 in vivo in an APP/APLP1 double knockout mouse background. We find that under these conditions cortical progenitors remain in their undifferentiated state much longer, displaying a higher number of mitotic cells. In addition, we show that neuron-specific APLP2 downregulation does not impact the speed or position of migrating excitatory cortical neurons. In summary, our data reveal that APLP2 is specifically required for proper cell cycle exit of neuronal progenitors, and thus has a distinct role in priming cortical progenitors for neuronal differentiation.
KU Leuven, Center for Human Genetics and Leuven Institute for Neurodegenerative Diseases, 3000 Leuven, Belgium.
S Ali M
SA
Shariati
Pierre
P
Lau
Bassem A
BA
Hassan
Ulrike
U
Müller
Carlos G
CG
Dotti
Bart
B
De Strooper
Annette
A
Gärtner
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002465:Cell Movement; D002478:Cells, Cultured; D018274:Electroporation; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011247:Pregnancy
D016564:Amyloid beta-Protein Precursor; C078201:Aplp1 protein, mouse; C492952:Aplp2 protein, mouse