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Artículo

Dosage of amyloid precursor protein affects axonal contact guidance in Down syndrome

Sosa, Lucas JavierIcon ; Postma, Nienke L.; Estrada-Bernal, Adriana; Hanna, M.; Guo, R.; Busciglio, Jorge; Pfenninger, Karl H.
Fecha de publicación: 01/2014
Editorial: Federation of American Societies for Experimental Biology
Revista: FASEB Journal
ISSN: 0892-6638
e-ISSN: 1530-6860
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Neurociencias

Resumen

Amyloid precursor protein (APP), encoded on Hsa21, functions as a cell adhesion molecule (CAM) in axonal growth cones (GCs) of the developing brain. We show here that axonal GCs of human fetal Down syndrome (DS) neurons (and of a DS mouse model) overexpress APP protein relative to euploid controls. We investigated whether DS neurons generate an abnormal, APP-dependent GC phenotype in vitro. On laminin, which binds APP and 1 integrins (Itgb1), DS neurons formed enlarged and faster-advancing GCs compared to controls. On peptide matrices that bind APP only, but not on those binding exclusively Itgb1 or L1CAM, DS GCs were significantly enlarged (2.0-fold), formed increased close adhesions (1.8-fold), and advanced faster (1.4-fold). In assays involving alternating stripes of monospecific matrices, human control GCs exhibited no preference for any of the substrates, whereas DS GCs preferred the APP-binding matrix (cross-over decreased significantly from 48.2 to 27.2%). Reducing APP expression in DS GCs with siRNA normalized most measures of the phenotype, including substrate choice. These experiments show that human DS neurons exhibit an APP-dependent, abnormal GC phenotype characterized by increased adhesion and altered contact guidance. The results suggest that APP overexpression may perturb axonal pathfinding and circuit formation in developing DS brain.
Palabras clave: BRAIN DEVELOPMENT , NEURODEVELOPMENTAL DISORDERS
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/130547
URL: https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.13-232686
DOI: http://dx.doi.org/10.1096/fj.13-232686
Colecciones
Articulos(CIQUIBIC)
Articulos de CENTRO DE INVEST.EN QCA.BIOL.DE CORDOBA (P)
Citación
Sosa, Lucas Javier; Postma, Nienke L.; Estrada-Bernal, Adriana; Hanna, M.; Guo, R.; et al.; Dosage of amyloid precursor protein affects axonal contact guidance in Down syndrome; Federation of American Societies for Experimental Biology; FASEB Journal; 28; 1; 1-2014; 195-205
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