Open AccessAPLP2 regulates neuronal stem cell differentiation during cortical development
Author(s) -
S. Ali M. Shariati,
Pierre Lau,
Bassem A. Hassan,
Ulrike Müller,
Carlos G. Dotti,
Bart De Strooper,
Annette Gärtner
Publication year - 2013
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.122440
Subject(s) - neurogenesis , biology , progenitor cell , microbiology and biotechnology , neuroscience , precursor cell , cellular differentiation , excitatory postsynaptic potential , gene silencing , neural stem cell , amyloid precursor protein , stem cell , cell , inhibitory postsynaptic potential , gene , medicine , genetics , disease , alzheimer's disease
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.
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