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Cortical development in the presenilin‐1 null mutant mouse fails after splitting of the preplate and is not due to a failure of reelin‐dependent signaling
Author(s) -
De Gasperi Rita,
Gama Sosa Miguel A.,
Wen Paul H.,
Li Jingjun,
Perez Gissel M.,
Curran Tom,
Elder Gregory A.
Publication year - 2008
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21661
Subject(s) - reelin , dab1 , reeler , biology , presenilin , phosphorylation , neuroscience , protein kinase b , pi3k/akt/mtor pathway , microbiology and biotechnology , psen1 , signal transduction , cancer research , medicine , alzheimer's disease , disease , extracellular matrix
Cortical development is disrupted in presenilin‐1 null mutant ( Psen1−/− ) mice. Prior studies have commented on similarities between Psen1−/− and reeler mice. Reelin induces phosphorylation of Dab1 and activates the phosphatidylinositol 3‐kinase (PI3K)/Akt pathway. Psen1 is known to modulate PI3K/Akt signaling and both known reelin receptors (apoER2 and VLDLR) are substrates for Psen1 associated γ‐secretase activity. The purpose of this study was to determine whether reelin signaling is disrupted in Psen1−/− mice. We show that, while Dab1 is hypophosphorylated late in cortical development in Psen1−/− mice, it is normally phosphorylated at earlier ages and reelin signaling is intact in Psen1−/− primary neuronal cultures. γ‐secretase activity was also not required for reelin‐induced phosphorylation of Dab1. Unlike reeler mice the preplate splits in Psen1−/− brain. Thus cortical development in Psen1−/− mice fails only after splitting of the preplate and is not due to an intrinsic failure of reelin signaling. Developmental Dynamics 237:2405–2414, 2008. © 2008 Wiley‐Liss, Inc.