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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.

ABSTRACT: 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 gamma-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. gamma-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.

SUBMITTER: De Gasperi R

PROVIDER: S-EPMC2566957 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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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.

De Gasperi Rita R Gama Sosa Miguel A MA Wen Paul H PH Li Jingjun J Perez Gissel M GM Curran Tom T Elder Gregory A GA

Developmental dynamics : an official publication of the American Association of Anatomists 20080901 9

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 gamma-secretase activity. The purpose of this study was to determine whether reelin signaling is disru ...[more]

PMID: 18729224

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Dataset Information

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.

Publications

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.

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