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Published on: March 18, 2014
The protocadherin gene Celsr3 is required for interneuron migration in the mouse forebrain
Guoxin Ying1, Sen Wu, Ruiqing Hou
1Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA.
Molecular and Cellular Biology
|April 1, 2009
Summary
The Celsr3 gene is crucial for the proper migration of cortical interneurons in the developing mouse brain. Loss of Celsr3 disrupts both tangential and radial migration, impacting neural circuit formation.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Mammalian brain interneurons are diverse and essential for neural circuitry.
- Most cortical interneurons originate in the subpallium and migrate long distances.
- Interneuron migration is critical for establishing functional brain networks.
Purpose of the Study:
- To investigate the role of the Celsr3 gene in mammalian interneuron migration.
- To determine how Celsr3 influences the development of cortical interneurons.
- To elucidate the molecular mechanisms underlying Celsr3-mediated interneuron migration.
Main Methods:
- Utilized a Celsr3 knockout mouse model with green fluorescent protein reporter.
- Analyzed Celsr3 expression in embryonic and adult mouse brains.
- Examined the distribution and laminar positioning of specific interneuron populations (calretinin- and calbindin-positive) in Celsr3 mutants.
- Investigated the expression of Neuregulin-1 (NRG1) and ErbB4 in Celsr3 mutant brains.
Main Results:
- Celsr3 is predominantly expressed in cortical interneurons and their germinal zones.
- Celsr3 knockout mice show reduced calretinin-positive interneurons in the neocortex, with accumulation at the corticostriatal boundary and increased presence in the striatum.
- The laminar distribution of calbindin-positive cells is significantly altered in Celsr3 mutants.
- Expression patterns of NRG1 and ErbB4 are dysregulated in Celsr3 mutant mice.
Conclusions:
- The protocadherin Celsr3 gene is essential for both tangential and radial migration of cortical interneurons.
- Celsr3 plays a class-specific role in directing interneuron migration pathways.
- Celsr3 influences interneuron migration likely through modulation of the NRG1/ErbB4 signaling pathway.
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