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Published on: March 4, 2015
A genetic interaction between the APP and Dab1 genes influences brain development.
Albéna Pramatarova1, Kelian Chen, Brian W Howell
1Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, 35 Convent Dr., Bethesda, MD 20892, USA.
Molecular and Cellular Neurosciences
|November 22, 2007
Summary
The amyloid precursor protein (APP) gene influences brain development by modulating the function of the Dab1 docking protein. APP constrains Dab1 activity, impacting neuronal organization and preventing developmental defects.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Dab1 docking protein is crucial for neuronal organization and Reelin signaling.
- The interaction between Dab1 and Amyloid Precursor Protein (APP) is known, but its functional significance in brain development is unclear.
Purpose of the Study:
- To investigate the genetic interaction between Dab1 and APP during brain development.
- To determine if APP influences Dab1 function and its role in neuronal positioning.
Main Methods:
- Utilized Dab1-hypomorphic animal models.
- Generated transgenic animals overexpressing a mutant form of APP (APPswe).
- Assessed phenotypes in the neocortex and cerebellum, including neuronal ectopias and Purkinje cell placement.
Main Results:
- Dab1-hypomorphic animals exhibited neocortical neuronal ectopias and reduced cerebellar volume.
- Overexpression of APPswe exacerbated these Dab1-related developmental defects.
- APP deficiency ameliorated the Dab1-hypomorphic phenotype in the cerebellum.
Conclusions:
- APP genetically interacts with Dab1, suggesting a regulatory role in brain development.
- APP acts to constrain the consequences of Dab1 activity during neuronal development.
- These findings highlight APP's influence on neuronal migration and lamination.
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