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Essential roles for the FE65 amyloid precursor protein-interacting proteins in brain development
Suzanne Guénette1, Yang Chang, Thomas Hiesberger
1Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA 02129-4404, USA. guenette@helix.mgh.harvard.edu
The EMBO Journal
|January 13, 2006
Summary
Targeted deletion of FE65 and FE65L1 adaptor proteins causes cortical dysplasia and brain developmental defects. These FE65 proteins are crucial for basement membrane assembly and APP-dependent signaling in the brain.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- FE65 and FE65L1 are adaptor proteins involved in neuronal development.
- Cortical dysplasia and lissencephaly are severe developmental brain disorders.
Purpose of the Study:
- To investigate the role of FE65 family adaptor proteins in cortical development.
- To elucidate the molecular mechanisms underlying FE65-mediated brain development.
Main Methods:
- Generation of FE65/FE65L1 compound null mice.
- Analysis of cortical structure, cell migration, and neuronal projections.
- Investigation of basement membrane assembly and protein interactions.
Main Results:
- FE65/FE65L1 double knockout mice exhibit cortical dysplasia, heterotopias, and aberrant projections.
- Disrupted pial basal membranes and impaired laminin organization were observed.
- Phenotype resembles that of APP family triple mutants, suggesting a link to APP-dependent signaling.
Conclusions:
- FE65 adaptor proteins are essential for proper basement membrane assembly during cortical development.
- FE65 proteins may mediate crucial signals from the APP family, impacting brain development.
- The Ena/Vasp protein family might also be involved in FE65-dependent developmental processes.
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