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Molecular and Cellular Biology, June 2009, p. 3045-3061, Vol. 29, No. 11
0270-7306/09/$08.00+0     doi:10.1128/MCB.00011-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Protocadherin Gene Celsr3 Is Required for Interneuron Migration in the Mouse Forebrain{triangledown}

Guoxin Ying,1 Sen Wu,2 Ruiqing Hou,3 Wei Huang,1 Mario R. Capecchi,1,2 and Qiang Wu1,3*

Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112,1 Howard Hughes Medical Institute, University of Utah, Salt Lake City, Utah 84112,2 Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China3

Received 5 January 2009/ Returned for modification 2 March 2009/ Accepted 20 March 2009

Interneurons are extremely diverse in the mammalian brain and provide an essential balance for functional neural circuitry. The vast majority of murine cortical interneurons are generated in the subpallium and migrate tangentially over a long distance to acquire their final positions. By using a mouse line with a deletion of the Celsr3 (Flamingo, or Fmi1) gene and a knock-in of the green fluorescent protein reporter, we find that Celsr3, a member of the nonclustered protocadherin (Pcdh) family, is predominantly expressed in the cortical interneurons in adults and in the interneuron germinal zones in embryos. We show that Celsr3 is crucial for interneuron migration in the developing mouse forebrain. Specifically, in Celsr3 knockout mice, calretinin-positive interneurons are reduced in the developing neocortex, accumulated in the corticostriatal boundary, and increased in the striatum. Moreover, the laminar distribution of cortical calbindin-positive cells is altered. Finally, we found that expression patterns of NRG1 (neuregulin-1) and its receptor ErbB4, which are essential for interneuron migration, are changed in Celsr3 mutants. These results demonstrate that the protocadherin Celsr3 gene is essential for both tangential and radial interneuron migrations in a class-specific manner.


* Corresponding author. Mailing address: Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China. Phone and fax: 86 21 34204300. E-mail: qwu123{at}gmail.com

{triangledown} Published ahead of print on 30 March 2009.


Molecular and Cellular Biology, June 2009, p. 3045-3061, Vol. 29, No. 11
0270-7306/09/$08.00+0     doi:10.1128/MCB.00011-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.