Essential roles for the FE65 amyloid precursor protein-interacting proteins in brain development

Suzanne Guénette, Yang Chang, Thomas Hiesberger, James A Richardson, Christopher B. Eckman, Elizabeth A. Eckman, Robert E Hammer, Joachim Herz

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Targeted deletion of two members of the FE65 family of adaptor proteins, FE65 and FE65L1, results in cortical dysplasia. Heterotopias resembling those found in cobblestone lissencephalies in which neuroepithelial cells migrate into superficial layers of the developing cortex, aberrant cortical projections and loss of infrapyramidal mossy fibers arise in FE65/FE65L1 compound null animals, but not in single gene knockouts. The disruption of pial basal membranes underlying the heterotopias and poor organization of fibrillar laminin by isolated meningeal fibroblasts from double knockouts suggests that FE65 proteins are involved in basement membrane assembly. A similar phenotype is observed in triple mutant mice lacking the APP family members APP, APLP1 and APLP2, all of which interact with FE65 proteins, suggesting that this phenotype may be caused by decreased transmission of an APP-dependent signal through the FE65 proteins. The defects observed in the double knockout may also involve the family of Ena/Vasp proteins, which participate in actin cytoskeleton remodeling and interact with the WW domains of FE65 proteins.

Original languageEnglish (US)
Pages (from-to)420-431
Number of pages12
JournalEMBO Journal
Volume25
Issue number2
DOIs
StatePublished - Jan 25 2006

Fingerprint

Amyloid beta-Protein Precursor
Brain
Proteins
Neuroepithelial Cells
Phenotype
Malformations of Cortical Development
Gene Knockout Techniques
Laminin
Actin Cytoskeleton
Basement Membrane
Fibroblasts
Organizations
Membranes
Actins
Animals
Genes
Defects
Fibers

Keywords

  • Alzheimer
  • APP
  • Axonal pathfinding
  • Heterotopia
  • Neuronal migration

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Essential roles for the FE65 amyloid precursor protein-interacting proteins in brain development. / Guénette, Suzanne; Chang, Yang; Hiesberger, Thomas; Richardson, James A; Eckman, Christopher B.; Eckman, Elizabeth A.; Hammer, Robert E; Herz, Joachim.

In: EMBO Journal, Vol. 25, No. 2, 25.01.2006, p. 420-431.

Research output: Contribution to journalArticle

Guénette, Suzanne ; Chang, Yang ; Hiesberger, Thomas ; Richardson, James A ; Eckman, Christopher B. ; Eckman, Elizabeth A. ; Hammer, Robert E ; Herz, Joachim. / Essential roles for the FE65 amyloid precursor protein-interacting proteins in brain development. In: EMBO Journal. 2006 ; Vol. 25, No. 2. pp. 420-431.
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