Independent and cooperative action of Psen2 with Psen1 in zebrafish embryos

Presenilin1 (PSEN1) and presenilin2 (PSEN2) are involved in the processing of type-l transmembrane proteins including the amyloid precursor protein (APP), Notch and several others. PSEN1 has been shown to be crucial for proteolytic cleavage of Notch in developing animal embryos. Mouse embryos lacking Psen1 function show disturbed neurogenesis and somite formation. resembling Notch pathway mutants. However, loss of Psen2 activity reveals only a minor phenotype. Zebrafish embryos are a valuable tool for analysis of the molecular genetic control of cell differentiation since endogenous gene expression call be modulated ill Subtle and complex ways to give a phenotypic readout. Using injection of morpholino antisense oligonucleotides to inhibit protein translation in zebrafish embryos, we show that reduced Psen2 activity decreases the number of melanocytes in the trunk but not in the Cranial area at 2 days post fertilisation (dpf). Reduced Psen2 activity apparently reduces Notch signalling resulting in perturbed spinal neurogenin1 (neurog1) expression, nenrogenesis and trunk and tail neural crest development. Similar effects are seen for reduced Psen1 activity. These results suggest that Psen2 plays a more prominent role in Notch signalling and embryo development in zebrafish than in mammals. Intriguingly, decreased Psen2 activity increases the number of Dorsal Longitudinal Ascending (DoLA) interneurons in the spinal cord while decreased Psen1 activity has no effect. However, the effect on Dol-As of reduced Psen2 can be ameliorated by Psen1 loss. The effects of changes in Psen2 activity on Dol-A interneurons and other cells in zebrafish embryos provide bioassays for more detailed dissection of Psen2 function. (C) 2009 Elsevier Inc. All rights reserved.