title: A genetic interaction between the APP and Dab1 genes influences brain development.
abstract: The Dab1 docking protein is required for the proper organization of brain laminae and for a signal transduction pathway initiated by Reelin binding to the ApoER2 and VLDLR receptors on the cell surface of neurons. Dab1 physically interacts with APP; however, it is not known whether the APP gene influences Dab1 function. Here we demonstrate a genetic interaction between Dab1 and APP. Dab1-hypomorphic animals have neuronal ectopias in the neocortex and reduced cerebellar volume, possibly a consequence of Purkinje cell misplacement. These phenotypes are exacerbated in transgenic animals overexpressing a mutant form of APP, APP(swe), which is characterized by increased processing at the beta-secretase site. The Dab1-hypomorphic phenotype is improved in the cerebellum of animals that are deficient for APP. Together this suggests that APP expression constrains the consequences of Dab1 activity during brain development.
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, 35 Convent Dr., Bethesda, MD 20892, USA.
authors.forename: Albéna
authors.initials: A
authors.lastname: Pramatarova
authors.forename: Kelian
authors.initials: K
authors.lastname: Chen
authors.forename: Brian W
authors.initials: BW
authors.lastname: Howell
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology* / Q000254:growth & development*; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D000091042:Reelin Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016564:Amyloid beta-Protein Precursor; C490897:Gab1 protein, mouse; D010750:Phosphoproteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse